0001104659-18-066801.txt : 20181108 0001104659-18-066801.hdr.sgml : 20181108 20181108064534 ACCESSION NUMBER: 0001104659-18-066801 CONFORMED SUBMISSION TYPE: 8-K PUBLIC DOCUMENT COUNT: 47 CONFORMED PERIOD OF REPORT: 20181108 ITEM INFORMATION: Results of Operations and Financial Condition ITEM INFORMATION: Submission of Matters to a Vote of Security Holders ITEM INFORMATION: Regulation FD Disclosure ITEM INFORMATION: Financial Statements and Exhibits FILED AS OF DATE: 20181108 DATE AS OF CHANGE: 20181108 FILER: COMPANY DATA: COMPANY CONFORMED NAME: Loxo Oncology, Inc. CENTRAL INDEX KEY: 0001581720 STANDARD INDUSTRIAL CLASSIFICATION: PHARMACEUTICAL PREPARATIONS [2834] IRS NUMBER: 462996673 STATE OF INCORPORATION: DE FISCAL YEAR END: 1231 FILING VALUES: FORM TYPE: 8-K SEC ACT: 1934 Act SEC FILE NUMBER: 001-36562 FILM NUMBER: 181168077 BUSINESS ADDRESS: STREET 1: 281 TRESSER BOULEVARD, 9TH FLOOR CITY: STAMFORD STATE: CT ZIP: 06901 BUSINESS PHONE: 203-653-3880 MAIL ADDRESS: STREET 1: 281 TRESSER BOULEVARD, 9TH FLOOR CITY: STAMFORD STATE: CT ZIP: 06901 8-K 1 a18-39556_18k.htm 8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

 

FORM 8-K

 

CURRENT REPORT PURSUANT TO

SECTION 13 OR 15(d) OF THE

SECURITIES EXCHANGE ACT OF 1934

 

Date of Report: November 8, 2018

(Date of earliest event reported)

 

LOXO ONCOLOGY, INC.

(Exact Name of Registrant as Specified in Its Charter)

 

Delaware

(State or Other Jurisdiction of Incorporation)

 

001-36562

 

46-2996673

(Commission File Number)

 

(IRS Employer Identification No.)

 

281 Tresser Blvd., 9th Floor
Stamford, CT

 

06901

(Address of Principal Executive Offices)

 

(Zip Code)

 

(203) 653-3880

(Registrant’s Telephone Number, Including Area Code)

 

Not Applicable

(Former name or former address, if changed since last report.)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company o

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. o

 

 

 


 

Item 2.02 Results of Operations and Financial Condition.

 

On November 8, 2018, Loxo Oncology, Inc. (“Loxo Oncology”) issued a press release announcing its financial results for the quarterly period ended September 30, 2018. A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K.

 

The information in this Item 2.02, including Exhibit 99.1 to this Current Report on Form 8-K, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended.  The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 shall not be incorporated by reference into any registration statement or other document filed by Loxo Oncology with the Securities and Exchange Commission, whether made before or after the date of this Current Report on Form 8-K, regardless of any general incorporation language in such filing (or any reference to this Current Report on Form 8-K generally), except as shall be expressly set forth by specific reference in such filing.

 

Item 5.07 Submission of Matters to a Vote of Security Holders.

 

This disclosure corrects our previous reporting under Item 5.07 of the Current Report on Form 8-K filed by Loxo Oncology on June 14, 2018 to report the results of proposal number 4, the non-binding advisory vote on the frequency of future advisory votes to approve named executive officer compensation. On June 13, 2018, the Company held its 2018 Annual Meeting of Stockholders and the following proposal was adopted:

 

4.              Adoption of a non-binding advisory vote on the frequency of future advisory votes to approve named executive officer compensation. The Company’s Board of Directors supported the advisory resolution, and will include a non-binding advisory shareholder vote on its executive compensation every year until the next vote on the frequency of shareholder votes on the compensation of executives.

 

One Year

 

Two Years

 

Three Years

 

Shares Abstaining

 

Broker Non-Votes

 

26,558,284

 

509,490

 

183,709

 

 

1,372,632

 

 

Item 7.01 Regulation FD.

 

Loxo Oncology is furnishing a copy of its current corporate presentation, which is attached hereto as Exhibit 99.2. Loxo Oncology undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.

 

The information furnished with this report, including Exhibit 99.2, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

 

Item 9.01 Financial Statements and Exhibits

 

(d) Exhibits.

 

Exhibit
Number

 

Description of Exhibit

99.1

 

Press release issued by Loxo Oncology regarding its financial results for the quarterly period ended September 30, 2018, dated November 8, 2018.

 

 

 

99.2

 

Corporate Presentation.

 

2


 

SIGNATURES

 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

 

Loxo Oncology, Inc.

 

 

 

 

 

 

 

Date: November 8, 2018

 

By:

/s/ Jennifer Burstein

 

 

Name:

Jennifer Burstein

 

 

Title:

Senior Vice President of Finance and principal financial officer

 

3


EX-99.1 2 a18-39556_1ex99d1.htm EX-99.1

Exhibit 99.1

 

 

Loxo Oncology Reports Third Quarter 2018 Financial Results

 

- Larotrectinib New Drug Application (NDA) PDUFA date is November 26, 2018 -

 

- LOXO-292 Registrational Data Expected in 2019 -

 

- LOXO-292 NDA Submission Expected in Late 2019 -

 

- Enrollment of First Patient in LOXO-305 Phase 1/2 Study on Track for Fourth Quarter 2018 -

 

STAMFORD, Conn., Nov. 08, 2018 — Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, today reported third quarter 2018 financial results.

 

“In the third quarter we made significant progress across our pipeline,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “At ESMO, larotrectinib investigators provided a comprehensive program update that included durability and additional response data in patients with TRK fusion cancers. Medical meeting updates for LOXO-292 in September and October showed encouraging ongoing durability of response for patients with RET-driven cancers. Taken together, these data have increased our conviction around a foundational company thesis—that selective, purpose-built medicines offer the best opportunity for durable efficacy and a manageable safety profile. In the fourth quarter, we look forward to LOXO-305, our fourth program, entering the clinic.”

 

Recent Highlights

 

Larotrectinib

 

·                  Conference presentations

 

·                  European Society for Medical Oncology (ESMO) 2018 Congress: On October 21, 2018, updated clinical data for larotrectinib were presented at ESMO. The oral presentation provided approximately one year of additional follow-up for the primary dataset, the 55 patients with TRK fusion cancer described in the larotrectinib New England Journal of Medicine publication from February 2018. In addition, the update included data for a supplementary dataset, an additional 67 patients with TRK fusion cancer who were subsequently enrolled across the larotrectinib development program. Response evaluations were based on investigator assessment. As of a data cut-off date of July 30, 2018, in the primary dataset (n=55), the overall response rate (ORR) was 80% (44/55) (95% CI: 67-90%) and in the supplementary dataset (n=67), the ORR was 81% (44/54) (95% CI: 69-91%). Across both datasets, the ORR was 81% (88/109) (95% CI: 72-88%). The ORR analyses for the supplementary and integrated datasets included nine patients with unconfirmed partial responses awaiting confirmatory response assessments, but did not include 13 patients who were awaiting an initial response assessment and continuing on study. Median duration of response (DOR) had not been reached in either the primary dataset or supplementary dataset, with median follow-up of 17.6 months and 7.4 months, respectively. Larotrectinib was well tolerated, with the majority of adverse events recorded as grade 1 or 2. The most common treatment-emergent adverse events occurring in 15% or more of patients in the trial were fatigue, dizziness, nausea, constipation, anemia, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), cough, diarrhea, vomiting, pyrexia, dyspnea, headache, myalgia and peripheral oedema. See the presented data here.

 


 

·                  Annual Meeting of the American Thyroid Association (ATA): On October 4, 2018, clinical data for patients with TRK fusion thyroid cancer enrolled in the larotrectinib development program were presented in an oral presentation at ATA. See the presented data here.

 

·                  International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer: On September 24, 2018, clinical data for patients with TRK fusion non-small cell lung cancer (NSCLC) enrolled in the larotrectinib development program were presented in a poster presentation at the IASLC World Conference on Lung Cancer. The poster can be found here.

 

·                  Molecular Analysis for Personalised Therapy 2018 Congress: On September 15, 2018, Ventana Medical Systems, Inc., a member of the Roche Group, and Loxo Oncology, presented a co-authored poster on the analytical validation of Ventana’s pan-TRK IHC assay at the Molecular Analysis for Personalised Therapy 2018 Congress. These data, in addition to other recently published evidence, suggest an annual incidence of approximately 2,500 to 3,000 cases of TRK fusion cancer in the United States. The poster can be found here.

 

·                  Integrative Therapies Program for Children with Cancer (ITPCC): On September 13, 2018, clinical data for children and adolescents with TRK fusion metastatic thyroid carcinoma enrolled in the larotrectinib development program were presented at the ITPCC conference. The poster can be found here.

 

·                  Publications

 

·                  Targeted Oncology Publication: On October 2, 2018, a manuscript was published online in Targeted Oncology detailing the potential effectiveness of TRK inhibition, including larotrectinib treatment, in patients with tumors harboring NTRK gene fusions, and the need for effective testing strategies. The publication can be found here.

 

·                  British Journal of Cancer Publication: On September 17, 2018, a case report was published in the British Journal of Cancer detailing a patient with TRK fusion high-grade glioma treated with larotrectinib. The publication can be found here.

 

·                  Cancer Publication: On September 11, 2018, a manuscript was published online in Cancer detailing the treatment of children with locally advanced TRK fusion sarcoma who were treated preoperatively with larotrectinib and underwent subsequent surgical resection. The publication can be found here.

 

·                  JCO Precision Oncology Publication: On August 2, 2018, a case report was published in JCO Precision Oncology detailing an adolescent patient with a TRK fusion undifferentiated sarcoma treated with larotrectinib. The publication can be found here.

 

·                  European Marketing Authorization Application (MAA): On August 27, 2018, Loxo Oncology and Bayer announced that Bayer had submitted an MAA for larotrectinib to the European Medicines Agency (EMA). More information can be found here.

 

LOXO-195

 

·                  LOXO-195 Orphan Drug Designation (ODD): In October, the U.S. Food and Drug Administration (FDA) granted ODD to LOXO-195 for the treatment of solid tumors with neurotrophic tyrosine receptor kinase (NTRK)-fusion proteins that have developed acquired resistance to prior TRK inhibitor therapy. The FDA’s Office of Orphan Drug Products grants orphan drug designation to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the United States. Orphan drug designation provides to Loxo Oncology certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

 


 

LOXO-292

 

·                  Annual Meeting of the ATA: On October 6, 2018, updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer were presented at the Annual Meeting of the ATA. The data presented were based on a July 19, 2018 data cut-off date and included the 29 patients with RET-mutant MTC and the nine patients with RET fusion-positive thyroid cancer who were included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting. With 3.5 months of additional follow-up since the ASCO presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity. Sixteen of 17 (94%) responding RET-mutant MTC patients remained on therapy and in response (median follow-up of 7.6 months for all 29 patients; median follow-up of 8.4 months for responding patients). Seven of seven (100%) responding RET fusion-positive thyroid remained on therapy and in response (median follow-up of 7.6 months for all nine patients; median follow-up of 8.5 months for responding patients). In RET-mutant MTC, the overall response rate was 59% (17/29) (95% CI: 39-77%) and the confirmed overall response rate was 56% (15/27) (95% CI: 35-75%). Of nine patients with RET fusion-positive thyroid cancer, the confirmed overall response rate was 78% (7/9) (95% CI: 40-97%). Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. See the presented data here.

 

·                  IASLC 19th World Conference on Lung Cancer: On September 25, 2018, updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET fusion-positive NSCLC were presented at the IASLC World Conference on Lung Cancer. The data presented were based on a July 19, 2018 data cut-off date and included the 38 patients with RET fusion-positive NSCLC who were initially included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting. With 3.5 months of additional follow-up since the ASCO presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity, with 25 of 26 (96%) responding RET fusion-positive NSCLC patients remaining on therapy and 24 of 26 (92%) remaining in response (median follow-up of 8.5 months for all 38 patients; median follow-up of 9.5 months for responding patients). The overall response rate was 68% (26/38) (95% CI: 51-83%) and the confirmed overall response rate was 68% (25/37) (95% CI: 50-82%). Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. See the presented data here.

 

·                  LOXO-292 Breakthrough Therapy Designations: The FDA granted three Breakthrough Therapy Designations to LOXO-292:

 

·                  for the treatment of patients with metastatic RET fusion-positive non-small cell lung cancer who require systemic therapy and have progressed following platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy;

 

·                  for the treatment of patients with RET-mutant medullary thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options; and for

 

·                  for the treatment of patients with advanced RET fusion-positive thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.

 

More information can be found here and here.

 

·                  LOXO-292 Orphan Drug Designation: In October, the FDA granted ODD to LOXO-292 for the treatment of pancreatic cancer. The FDA’s Office of Orphan Drug Products grants orphan drug designation to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the United States. Orphan drug designation provides to Loxo Oncology certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

 


 

LOXO-305

 

·                  Society of Hematologic Oncology (SOHO) Annual Meeting: On September 12, 2018, preclinical characterization data for LOXO-305 were presented at the SOHO Annual Meeting. The poster can be found here.

 

Third Quarter 2018 Financial Results

 

As of September 30, 2018, Loxo Oncology had aggregate cash, cash equivalents and investments of $647.6 million, compared to $626.2 million as of December 31, 2017.

 

Revenue from the collaboration agreement was $42.5 million for the third quarter of 2018, compared to none for the third quarter of 2017. This represents $52.9 million in revenue recognized from the $400.0 million upfront payment from the Bayer collaboration offset by $10.5 million, Loxo Oncology’s share of the joint larotrectinib co-promotion costs in the same period.

 

Revenue from the collaboration agreement was $123.5 million for the nine months ended September 30, 2018, compared to none for the nine months ended September 30, 2017. This represents $147.0 million in revenue recognized from the $400.0 million upfront payment from the Bayer collaboration offset by $23.5 million, Loxo Oncology’s share of the joint larotrectinib co-promotion costs in the same period. Loxo Oncology recognizes revenue from the upfront payment on a proportional performance basis utilizing a calculation based on quarterly research and development spending associated with larotrectinib and LOXO-195, relative to cumulative and forecasted research and development spending on larotrectinib and LOXO-195 over the course of the collaboration agreement. As a result, the quarterly revenue recognized for the upfront payment varies from quarter to quarter. A supporting schedule that shows the different components of revenue from the collaboration agreement is included with the attached financial statements.

 

Research and development expenses were $56.9 million for the third quarter of 2018 compared to $64.8 million for the third quarter of 2017. This decrease was primarily due to a non-recurring charge related to the $40.0 million asset acquisition of the BTK inhibitor program from Redx in the third quarter of 2017, offset by expanded development expenses across the LOXO-292 and LOXO-305 programs and higher employment costs primarily due to increased headcount. These numbers are net of 50/50 cost-sharing with Bayer for larotrectinib and LOXO-195 development costs. Loxo Oncology recognized research and development-related stock-based compensation expense of $4.2 million during the third quarter of 2018 as compared to $2.1 million for the third quarter of 2017.

 

Research and development expenses were $130.5 million for the nine months ended September 30, 2018 compared to $109.3 million for the nine months ended September 30, 2017. This increase was primarily due to expanded development expenses across the LOXO-292 and LOXO-305 programs and higher employment costs primarily due to increased headcount. These numbers are net of 50/50 cost-sharing with Bayer for larotrectinib and LOXO-195 development costs. Loxo Oncology recognized research and development-related stock-based compensation expense of $14.3 million during the nine months ended September 30, 2018 as compared to $8.0 million for the nine months ended September 30, 2017.

 

General and administrative expenses were $15.9 million for the third quarter of 2018 compared to $9.7 million for the third quarter of 2017. The increase was primarily due to additional headcount, associated employment costs, and general and administrative professional fees. Loxo Oncology recognized general and administrative-related stock-based compensation expense of $6.9 million during the third quarter of 2018 compared to $3.1 million for the third quarter of 2017.

 


 

General and administrative expenses were $43.8 million for the nine months ended September 30, 2018 compared to $21.0 million for the nine months ended September 30, 2017. The increase was primarily due to additional headcount, associated employment costs, and general and administrative professional fees. Loxo Oncology recognized general and administrative-related stock-based compensation expense of $18.8 million during the nine months ended September 30, 2018 compared to $6.7 million for the nine months ended September 30, 2017.

 

Net loss was $27.1 million and $42.3 million for the three and nine months ended September 30, 2018, respectively, compared to $73.3 million and $128.2 million for the three and nine months ended September 30, 2017, respectively. This decrease in net loss was primarily driven by the revenue recognized from the $400.0 million upfront payment from the Bayer collaboration, the larotrectinib and LOXO-195 development reimbursement from the Bayer collaboration, offset by increases in operating expenses.

 

Non-GAAP net loss was $68.8 million and $156.2 million for the three and nine months ended September 30, 2018, respectively, compared to $28.1 million and $73.6 million for the three and nine months ended September 30, 2017, respectively. This non-GAAP net loss measure, more fully described below under “Non-GAAP Financial Measures,” excludes the recognition of collaboration revenue related to the Bayer upfront payment and share-based compensation expenses. A reconciliation of the GAAP financial results to non-GAAP financial results is included with the attached financial statements.

 

Earnings Conference Call and Webcast Information 
Loxo Oncology will host a conference call today at 8:00 a.m. ET to discuss the third quarter 2018 financial results and company updates. A live webcast can be accessed under “Events & Presentations” in the Investors & Media section of the company’s website at www.loxooncology.com. The conference call can be accessed by dialing (877) 930-8065 (domestic) or (253) 336-8041 (international) and referring to conference ID 8379404. The webcast will be archived and made available for replay on the company’s website beginning approximately two hours after the event.

 

About Loxo Oncology
Loxo Oncology is a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers. Our pipeline focuses on cancers that are uniquely dependent on single gene abnormalities, such that a single drug has the potential to treat the cancer with dramatic effect. We believe that the most selective, purpose-built medicines have the highest probability of maximally inhibiting the intended target, with the intention of delivering best-in-class disease control and safety. Our management team seeks out experienced industry partners, world-class scientific advisors and innovative clinical-regulatory approaches to deliver new cancer therapies to patients as quickly and efficiently as possible. For more information, please visit the company’s website at www.loxooncology.com.

 

Forward Looking Statements 
This press release contains “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: “anticipate,” “intend,” “plan,” “goal,” “seek,” “believe,” “project,” “estimate,” “expect,” “strategy,” “future,” “likely,” “may,” “should,” “will” and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, the reporting, timing and success of our clinical trials, the success of our efforts to commercialize larotrectinib, and the timing or success of regulatory approvals in the U.S. and in the E.U. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Annual Report on Form 10-K, and other reports as filed from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement,

 


 

whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

 

Non-GAAP Financial Measures
This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and also certain historical non-GAAP financial measures. In particular, we have provided non-GAAP net loss, adjusted to exclude recognized collaboration revenue related to an upfront payment, the acquisition of an in process R&D asset and share-based compensation expenses. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. For a reconciliation of these non-GAAP financial measures to their most directly comparable GAAP financial measure, see the table below. Non-GAAP financial measures may not be comparable to similarly titled measures reported by other companies, since not all companies may calculate these measures in an identical manner and, therefore, it is not necessarily an accurate measure of comparison between companies. However, we believe the presentation of non-GAAP net loss, when viewed in conjunction with our GAAP results, provides investors and management with a more complete understanding of our ongoing and projected operating performance because this measure excludes the recognition of collaboration revenue from an upfront payment and the acquisition of an in process R&D asset that are non-recurring events and non-cash charges that are substantially dependent on changes in the market price of our common stock. We believe our non-GAAP net loss measure helps indicate underlying trends in our business and is important in comparing current results with prior period results.

 


 

Financials

 

LOXO ONCOLOGY, INC.

Condensed Consolidated Balance Sheets

(in thousands, except share and per share amounts)

 

 

 

 

September 30,

 

December 31,

 

 

 

2018

 

2017

 

 

 

(Unaudited)

 

 

 

Assets

 

 

 

 

 

Cash, cash equivalents and investments

 

$

647,602

 

$

626,200

 

Receivable from collaboration partner

 

 

150,000

 

Other prepaid expenses and current assets

 

6,309

 

5,607

 

Property and equipment, net

 

4,253

 

912

 

Other assets

 

1,064

 

723

 

Total assets

 

659,228

 

783,442

 

 

 

 

 

 

 

Liabilities and stockholders’ equity

 

 

 

 

 

Accounts payable

 

2,018

 

3,996

 

Payable due to collaboration partner

 

2,576

 

 

Accrued expenses and other current liabilities

 

43,739

 

22,537

 

Deferred revenue

 

231,680

 

378,699

 

Total liabilities

 

280,013

 

405,232

 

Commitments and contingencies

 

 

 

 

 

Stockholders’ equity

 

 

 

 

 

Common stock, $0.0001 par value; 125,000,000 shares authorized; 30,566,797 and 29,991,884 shares issued and outstanding at September 30, 2018 and December 31, 2017, respectively

 

3

 

3

 

Additional paid-in capital

 

710,137

 

666,891

 

Accumulated deficit

 

(330,460

)

(288,112

)

Other comprehensive loss

 

(465

)

(572

)

Total stockholders’ equity

 

379,215

 

378,210

 

Total liabilities and stockholders’ equity

 

$

659,228

 

$

783,442

 

 


 

LOXO ONCOLOGY, INC.

Consolidated Statements of Operations

(unaudited)

(in thousands, except share and per share amounts)

 

 

 

Three Months Ended
September 30,

 

Nine Months Ended
September 30,

 

 

 

2018

 

2017

 

2018

 

2017

 

 

 

 

 

 

 

 

 

 

 

Revenue from collaboration agreement

 

$

42,470

 

$

 

$

123,500

 

$

 

 

 

 

 

 

 

 

 

 

 

Operating expenses:

 

 

 

 

 

 

 

 

 

Research and development

 

56,928

 

64,754

 

130,473

 

109,321

 

General and administrative

 

15,864

 

9,680

 

43,800

 

20,968

 

Total operating expenses

 

72,792

 

74,434

 

174,273

 

130,289

 

Loss from operations

 

(30,322

)

(74,434

)

(50,773

)

(130,289

)

Interest income, net

 

3,258

 

1,115

 

8,425

 

2,041

 

Net loss

 

$

(27,064

)

$

(73,319

)

$

(42,348

)

$

(128,248

)

 

 

 

 

 

 

 

 

 

 

Per share information:

 

 

 

 

 

 

 

 

 

Net loss per share of common stock, basic and diluted

 

$

(0.89

)

$

(2.45

)

$

(1.40

)

$

(4.68

)

Weighted average shares outstanding, basic and diluted

 

30,502,789

 

29,872,198

 

30,230,160

 

27,391,020

 

 


 

LOXO ONCOLOGY, INC.

Reconciliation of GAAP Net Loss to Non-GAAP Net Loss

(unaudited)

(in thousands, except share and per share amounts)

 

 

 

Three Months Ended
September 30,

 

Nine Months Ended
September 30,

 

 

 

2018

 

2017

 

2018

 

2017

 

 

 

 

 

 

 

 

 

 

 

GAAP net loss

 

$

(27,064

)

$

(73,319

)

$

(42,348

)

$

(128,248

)

Adjustments:

 

 

 

 

 

 

 

 

 

Revenue from collaboration agreement

 

 

 

 

 

 

 

 

 

Revenue recognized from $400M upfront payment

 

(52,938

)

 

(147,019

)

 

 

 

 

 

 

 

 

 

 

 

Acquisition of in process R&D (IPR&D) asset included in R&D expenses

 

 

40,000

 

 

40,000

 

 

 

 

 

 

 

 

 

 

 

Share-based compensation expenses included in R&D expenses

 

4,205

 

2,148

 

14,313

 

8,010

 

Share-based compensation expenses included in G&A expenses

 

6,948

 

3,120

 

18,837

 

6,667

 

Total share-based compensation expenses

 

11,153

 

5,268

 

33,150

 

14,667

 

 

 

 

 

 

 

 

 

 

 

Total adjustments

 

(41,785

)

45,268

 

(113,869

)

54,667

 

Non-GAAP net loss

 

$

(68,849

)

$

(28,051

)

$

(156,217

)

$

(73,571

)

 

 

 

 

 

 

 

 

 

 

Per share information:

 

 

 

 

 

 

 

 

 

Net loss per share of common stock, basic and diluted

 

$

(2.26

)

$

(0.94

)

$

(5.17

)

$

(2.69

)

Weighted average shares outstanding, basic and diluted

 

30,502,789

 

29,872,198

 

30,230,160

 

27,391,020

 

 


 

LOXO ONCOLOGY, INC.

Calculation of Revenue from Collaboration Agreement

(unaudited)

(in thousands)

 

 

 

Three Months Ended
September 30,

 

Nine Months Ended
September 30,

 

 

 

2018

 

2017

 

2018

 

2017

 

 

 

 

 

 

 

 

 

 

 

Upfront payment

 

 

 

 

 

 

 

 

 

Revenue recognized from $400M upfront payment

 

$

52,938

 

$

 

$

147,019

 

$

 

 

 

 

 

 

 

 

 

 

 

Milestones

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Royalties

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Co-promote

 

 

 

 

 

 

 

 

 

Product revenue subject to profit sharing (as recorded by Bayer)

 

 

 

 

 

Combined cost of goods sold, distribution, selling, general and administrative expenses

 

(20,936

)

 

(47,038

)

 

Combined collaboration co-promotion profit/(loss)

 

(20,936

)

 

(47,038

)

 

 

 

 

 

 

 

 

 

 

 

Loxo Oncology’s 50/50 share of collaboration co-promotion profit/(loss)

 

(10,468

)

 

(23,519

)

 

 

 

 

 

 

 

 

 

 

 

Total revenue from collaboration agreement

 

$

42,470

 

$

 

$

123,500

 

$

 

 

# # #

 

Contacts for Loxo Oncology, Inc.

 

Company:
Lauren Cohen
Director, Corporate Communications
lcohen@loxooncology.com

 

Investors:
Peter Rahmer
Endurance Advisors, LLC
415-515-9763
prahmer@enduranceadvisors.com

 

Media:
Dan Budwick
1AB Media
973-271-6085
dan@1abmedia.com

 


EX-99.2 3 a18-39556_1ex99d2.htm EX-99.2

Exhibit 99.2

Corporate Presentation

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Forward Looking Statements This presentation and the accompanying oral presentation contain “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future, "likely," "may," "should," "will" and similar references to future periods. Examples of forward-looking statements include, among others, statements we make regarding our future financial performance, business plans and objectives, timing and success of our clinical trials, our ability to obtain regulatory approval or the timing of regulatory filings, the potential therapeutic benefits and economic value of our product candidates, potential growth opportunities, the timing or success of commercialization, our partnership with Bayer, financing plans, competitive position and industry environment. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: those related to our future financial performance, our ability to raise additional funding when needed, our ability to develop and maintain partnerships, our ability to identify and develop new products in a timely manner, the outcome, cost and timing of our product development activities and clinical trials, market size and acceptance of our targeted small molecule therapeutics and diagnostics, our ability to maintain, protect and enhance our brand and intellectual property, our ability to continue to stay in compliance with applicable laws and regulations, our ability to scale our business and make key hires and such other factors as discussed under the section titled “Risk Factors” and elsewhere in our annual report on Form 10-K and quarterly reports on Form 10-Q that we filed with the Securities and Exchange Commission (“SEC”) as well as our other filings and the documents incorporated by reference therein, with the SEC. Any forward-looking statement made by us in this presentation and the accompanying oral presentation is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. Certain information in this slide deck regarding our product candidates is derived from information provided by industry sources. We believe such information is accurate and that the sources from which is has been obtained are reliable. However, we cannot guarantee the accuracy of, and have not independently verified such information. 2

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Our Approach Loxo Oncology builds highly selective medicines designed to target genomically defined cancers Each of our clinical programs meets the following criteria: The genomic alteration in question is an oncogenic driver, not a mere passenger event in the cancer cell We believe we can develop a selective medicine with best-in-class potential Patients with the alteration can be identified through testing 3

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Building the Loxo Oncology Pipeline 4 In-house R&D In-licensing & Acquisitions Discovery Collaborations

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Pipeline of Highly Selective Drug Candidates for Genomically Defined Cancers 5 Program Indication Stage of Development Eligible US patients/yr1 Preclinical Phase 1 Phase 2 Marketed Status Larotrectinib (LOXO-101) TRK fusion cancers Nov 2018 PDUFA Date MAA submitted* 2,500-3,000 LOXO-292 Cancers with RET fusions and RET mutant MTC Registrational data expected in 2019 NDA submission expected late 2019 ~5,000 LOXO-195 Next-generation TRK inhibitor for acquired resistance Ph. 1 ongoing Data update expected in first half 2019 2,500-3,000 LOXO-305 Non-covalent BTK inhibitor for B-cell malignancies with acquired resistance to covalent BTK inhibitors Ph. 1 initiation expected in 4Q 2018 Next-Generation RET Inhibitor For potential acquired resistance Candidate-seeking FGFR2/3 Cancers with FGFR2/3 alterations Lead optimization ongoing 1 Estimated number of eligible patients with advanced cancer per year in U.S. * Per partnership agreement, MAA is handled by Bayer.

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6 Larotrectinib (TRK)

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Bayer Global Partnership for TRK Franchise 7 Global partnership with Bayer to develop and commercialize larotrectinib and LOXO-195, announced November 14, 2017 Up to $1.55B in upfront, regulatory, and commercial milestones Loxo will lead global development activities and U.S. regulatory activities Development costs shared 50/50 globally In the U.S., Loxo and Bayer will co-promote the products and share commercial costs and profits on a 50/50 basis Bayer will lead ex-U.S. regulatory activities and worldwide commercial activities Bayer will pay tiered, double-digit royalties on ex-U.S. net sales

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TRK Fusions Found in Diverse Cancer Histologies 8 Brain cancers (glioma, GBM, astrocytoma) Salivary (MASC) Lung cancer Secretory breast cancer Melanoma Colon Sarcoma (multiple) Infantile fibrosarcoma Gliomas Thyroid cancer Congenital nephroma Sarcoma (multiple) Common cancer with low TRK fusion frequency Rare cancer with high TRK fusion frequency Cholangiocarcinoma Pancreatic GIST Thyroid cancer Spitz nevi Estimated 2,500–3,000 patients harbor TRK fusion-positive cancers in the United States annually

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Larotrectinib TRK Fusion Development Program (ESMO 2018) Adult phase I Age 18 years Advanced solid tumors SCOUT: pediatric phase I/II Age 21 years Advanced solid tumors NAVIGATE: adult/adolescent phase II ‘basket’ trial Age 12 years Advanced solid tumors TRK fusion cancer TRK fusion status determined by local CLIA (or similarly accredited) laboratories Primary endpoint Best objective response rate (RECIST 1.1) Secondary endpoints Duration of response Progression-free survival Safety Dosing Single-agent larotrectinib, administered predominantly at 100 mg BID continuously Treatment beyond progression permitted if patient continuing to benefit 122 patients with TRK fusion cancer Primary Supplementary n=2 n=25 n=8 n=12 n=55 n=67 n=40 n=35 Data cutoff: 30 July 2018 BID, twice-daily; CLIA, clinical laboratory improvement amendments; RECIST, Response Evaluation Criteria In Solid Tumors 9

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Primary Dataset: Larotrectinib Has Proven Efficacy in TRK Fusion Cancer (ESMO 2018) 17 Jul 2017 (n=55) 30 July 2018 (n=55) ORR (95% CI)† 80% (6790%) 80% (6790%) Best response† PR 64% 62% CR 16% 18% # *Patient had TRKC solvent front resistance mutation (G623R) at baseline due to prior therapy; #Surgical CR; †RECIST 1.1 Note: One patient not shown here. The patient discontinued treatment prior to any post-baseline tumor measurements. CR, complete response; ORR, objective response rate; PR, partial response * Maximum change in tumor size (%) Infantile fibrosarcoma Gastrointestinal stromal tumor Thyroid Salivary gland Melanoma Breast Lung Appendix Soft tissue sarcoma Colon Pancreas Cholangiocarcinoma 93.2 Investigator response assessments, as of 30 July 2018 10 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50

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Supplementary Dataset: Larotrectinib Efficacy Consistent with Primary Dataset (ESMO 2018) Primary (n=55) Supplementary* (n=54) ORR (95% CI)† 80% (6790%) 81% (6991%) Best response† PR 62% 65% CR 18% 17% Infantile fibrosarcoma Gastrointestinal stromal tumor Thyroid Salivary gland Congenital mesoblastic nephroma Unknown primary Lung Soft tissue sarcoma Colon Bone sarcoma Melanoma # Maximum change in tumor size (%) *Evaluable patients; includes 9 unconfirmed PRs pending confirmation; does not include 13 patients continuing on study and awaiting initial response assessment; #Surgical CR; †RECIST 1.1 Note: One patient not shown here. The patient discontinued treatment prior to any post-baseline tumor measurements. CR, complete response; ORR, objective response rate; PR, partial response Investigator response assessments, as of 30 July 2018 11

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Integrated Dataset: Larotrectinib is Efficacious Regardless of Tumor Type (ESMO 2018) Infantile fibrosarcoma Soft tissue sarcoma Thyroid Salivary gland Melanoma Breast Lung Appendix Gastrointestinal stromal tumor Colon Pancreas Cholangiocarcinoma Congenital mesoblastic nephroma Unknown primary Bone sarcoma Maximum change in tumor size (%) ‡Includes 9 unconfirmed PRs pending confirmation; does not include 13 patients continuing on study and awaiting initial response assessment *Patient had TRKC solvent front resistance mutation (G623R) at baseline due to prior therapy; #Surgical CR; †RECIST 1.1 Note: Two patients not shown here. These patients discontinued treatment prior to any post-baseline tumor measurements. CR, complete response; ORR, objective response rate; PR, partial response Investigator response assessments, as of 30 July 2018 Integrated‡ (n=109) ORR (95% CI)† 81% (7288%) Best response† PR 63% CR 17% # 93.2 # * # 12

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Integrated Dataset: Larotrectinib is Efficacious Regardless of Age (ESMO 2018) Maximum change in tumor size (%) ‡Includes 9 unconfirmed PRs pending confirmation; does not include 13 patients continuing on study and awaiting initial response assessment ͌Age <21 years *Patient had TRKC solvent front resistance mutation (G623R) at baseline due to prior therapy; #Surgical CR; †RECIST 1.1 Note: Two patients not shown here. These patients discontinued treatment prior to any post-baseline tumor measurements. CR, complete response; ORR, objective response rate; PR, partial response Investigator response assessments, as of 30 July 2018 Adult patients Pediatric patients ͌ Integrated‡ (n=109) ORR (95% CI)† 81% (7288%) Best response† PR 63% CR 17% # 93.2 # * # 13

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Overall treatment duration (months) Median time to response = 1.8 months Integrated Dataset (n=122): Duration of Larotrectinib Treatment (ESMO 2018) Treatment after progression Treatment after surgery Surgical CR Treatment ongoing n=122 patients 84% of responding patients and 73% of all patients remain on treatment or underwent surgery with curative intent Investigator response assessments, as of 30 July 2018 CR, complete response 14

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Sustained Responses with Larotrectinib: Duration of Response (ESMO 2018) 0.75 Median follow-up 17.6 months Median DOR not reached 88% 75% Probability Months from start of response 1 0.5 0.25 0 0 6 12 18 24 30 36 42 44 No. at risk: 35 29 13 9 4 1 0 0.75 93% 81% 1 0.5 0.25 0 0 12 6 9 3 15 18 35 4 18 12 27 0 0 Median follow-up 7.4 months Median DOR not reached No. at risk: Primary dataset* Supplementary dataset* Kaplan-Meier landmark analysis 17 Jul 2017 30 July 2018 6 months 83% 88% 12 months 71% 75% Probability Months from start of response *In patients with confirmed complete or partial responses DOR, duration of response Investigator response assessments, as of 30 July 2018 15

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Adverse Events with Larotrectinib: 15% in Safety Database (n=207) (ESMO 2018) 11 (9%) of 122 patients with TRK fusion cancer required dose reductions – all maintained tumor regression on reduced dose 1 (<1%) of 122 patients with TRK fusion cancer discontinued larotrectinib due to an adverse event As of 30 July 2018 AEs, adverse events; ALT, alanine aminotransferase; AST, aspartate aminotransferase Treatment-emergent AEs (%) Treatment-related AEs (%) Grade 1 Grade 2 Grade 3 Grade 4 Total Grade 3 Grade 4 Total Fatigue 18 15 3 – 36 <1 – 18 Dizziness 25 3 1 – 29 <1 – 21 Nausea 24 3 1 – 29 1 – 15 Constipation 22 5 <1 – 27 – – 12 Anemia 10 7 10 – 27 2 – 11 ALT increased 17 5 3 <1 26 2 <1 21 AST increased 18 5 3 – 26 1 – 19 Cough 23 3 <1 – 26 – – 1 Diarrhea 16 6 1 – 23 – – 5 Vomiting 17 6 <1 – 23 – – 10 Pyrexia 12 5 <1 <1 18 – – 1 Dyspnea 10 6 2 – 18 – – 1 Headache 13 4 – – 16 – – 4 Myalgia 12 3 1 – 16 <1 – 7 Peripheral oedema 12 4 – – 15 – – 7 16

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Larotrectinib Regulatory Timing Breakthrough therapy designation (BTD) granted in July 2016 BTD indication: “For the treatment of unresectable or metastatic solid tumors with NTRK-fusion proteins in adult and pediatric patients who require systemic therapy and who have either progressed following prior treatment or who have no acceptable alternative treatments” Rolling NDA submission completed in March 2018 PDUFA date Nov 26, 2018 MAA submitted on August 27, 2018* Potential for larotrectinib to be the first new cancer drug approved with a genomically-defined, tumor-agnostic indication * Per partnership agreement, MAA is handled by Bayer. 17

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18 LOXO-195 (TRK)

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LOXO-195: Structurally Distinct, Similarly Selective 19 LOXO-195 Larotrectinib TRKB TRKB TRKA TRKA

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LOXO-195 to Address TRK Acquired Resistance 20 TRKA G595R TRK solvent front mutations detected in 7 of 9 patients with acquired resistance. First 2 patients successfully treated with LOXO-195. LOXO-195 Treatment Larotrectinib LOXO-195 Baseline On Treatment Tumor type Fusion Resistance mutation NSCLC TPR-NTRK1 TRKA G595R + TRKA G667S Colorectal LMNA-NTRK1 TRKA G595R Cholangio LMNA-NTRK1 TRKA F589L Pancreas CTRC-NTRK1 TRKA A608D Thyroid IRFBP2-NTRK1 TRKA G595R Colorectal TPM3-NTRK1 TRKA G595R + TRKA F589L Salivary ETV6-NTRK3 Not tested Sarcoma TPM3-NTRK1 TRKA G595R GIST ETV6-NTRK3 TRKC G623R + TRKC G696A IFS ETV6-NTRK3 TRKC G623R Drilon A, Cancer Discovery, Online First (03-JUNE-2017) Drilon et al. Efficacy of Larotrectinib in TRK Fusion – Positive Cancers in Adults and Children. N Engl J Med 2018;378:731-9. DOI: 10.1056/NEJMoa1714448. July 2017 data cut-off date

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LOXO-195 Clinical Development Phase 1/2 trial enrolling Next clinical data update expected in first half 2019 Plan to address patients with TRK fusion cancers harboring solvent front mutations, xDFG mutations, and gatekeeper mutations Loxo Oncology is well-positioned to be the first oncology company to simultaneously develop a first-generation inhibitor and a second-generation inhibitor to address acquired resistance 21

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22 LOXO-292 (RET)

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Activation of RET in Cancer 23 Drilon et al. Nat Rev Clin Oncol 2018;15:151–67; Kato et al. Clin Cancer Res 2017; 23:1988–97; Pietrantonio et al. Ann Oncol 2018;Mar 10; Su et al. PLoS One 2016;11(11)

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Cabozantinib Vandetanib Lenvatinib Alectinib *cellular (phospho-RET) inhibitory concentration corrected for human plasma protein binding and published human PK RET KDR/VEGFR2 MET/ALK/ROS Other kinases FGFR1-3/EGFR MKI Approved Dose Toxicities Cabozantinib 140 mg QD Diarrhea, PPE, weight/appetite, fatigue, hypertension 51% Vandetanib 300 mg QD Diarrhea, hypertension, QT prolonged, fatigue, rash 24% Lenvatinib 24 mg QD Diarrhea, hypertension, weight/appetite, fatigue, proteinuria 47% Alectinib 600 mg BID ALT/AST/GGT/Bilirubin, anemia, nausea/vomiting, diarrhea 32% RET Inhibition (Human Cmax)* Repurposed “RET Inhibitors”: Poor RET Coverage in Humans 24 Drilon et al. IASLC 2017. Abstract 10955.

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LOXO-292: A Potent and Selective RET Inhibitor 25 Subbiah et al. Ann Oncol 2018; Cabo = cabozantinib; PDX = patient-derived xenograft; NSCLC = non-small cell lung cancer; CRCA = colorectal cancer; MTC = medullary thyroid cancer; BID = twice-daily; QD = once-daily

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LIBRETTO-001: Phase 1 Dose Escalation and Pharmacokinetics (WCLC & ATA 2018) 26 82 patients enrolled across 8 dose levels QD = once-daily; BID = twice-daily; PK = pharmacokinetics Patients enrolled as of April 2, 2018

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LIBRETTO-001: Patient Demographics and Molecular Features (WCLC & ATA 2018) 27 NSCLC = non-small-cell lung cancer; MTC = medullary thyroid cancer; 1 cabozantinib, vandetanib, or other MKI; 2 Brain metastasis in RET fusion-positive thyroid cancer; Patients enrolled as of April 2, 2018 Tumor type, n (%) Total (n=82) RET fusion-positive NSCLC RET fusion-positive thyroid cancer RET fusion-positive pancreatic cancer RET-mutant MTC No known activating RET alteration 38 (46%) 9 (11%) 2 (2%) 29 (35%) 4 (5%) Characteristic Total (n=38) Female / Male, n (%) 16 (42) / 22 (58) Median age (range), years 55.5 (17-88) ECOG performance status, n (%) 0 1 2 14 (37) 22 (58) 2 (5) Tumor type, n (%) RET-mutant MTC RET fusion-positive thyroid cancer 29 (76) 9 (24) Median prior systemic regimens (range) 3 (1-7) RET-mutant MTC Prior cabozantinib or vandetanib Prior cabozantinib and vandetanib 23 (79) 13 (45) RET fusion-positive thyroid cancer Prior radioactive iodine (RAI), n (%) Prior sorafenib or lenvatinib, n (%) 7 (78) 7 (78) Brain metastases, n (%)2 4 (44) RET-altered thyroid cancers Characteristic Total (n=38) Female / Male, n (%) 22 (58) / 16 (42) Median age (range), years 62.5 (36–80) ECOG performance status, n (%) 0 1 6 (16) 32 (84) Median prior systemic regimens (range) 3 (1–9) Prior multikinase inhibitor (MKI), n (%)1 0 1 17 (45) 21 (55) Prior chemotherapy or immunotherapy, n (%) 33 (87) Prior chemotherapy and immunotherapy, n (%) 15 (39) Brain metastases, n (%) 8 (21) RET-fusion positive NSCLC

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LOXO-292 Safety Profile (WCLC & ATA 2018) 28 All doses and patients, n=82 Treatment-emergent AEs (10% overall) Treatment-related AEs Grade 1 Grade 2 Grade 3 Grade 4 Total Grade 3 Grade 4 Total Diarrhea 15% 7% 1% – 23% 1% – 11% Fatigue 9% 13% – – 22% – – 17% Dry Mouth 21% – – – 21% – – 13% Constipation 17% 2% – – 20% – – 4% Hypomagnesemia 12% 1% – – 13% – – 2% Cough 11% 1% – – 12% – – 1% Headache 10% 1% 1% – 12% – – 1% Nausea 9% 4% – – 12% – – 5% 8 treatment-emergent AEs, regardless of attribution, in 10% of patients; most were Grade 1 and judged not related to LOXO-292 Four patients experienced treatment-related AEs  grade 3 (all grade 3): diarrhea, increased ALT/AST, thrombocytopenia (DLT @ 240mg BID), tumor lysis syndrome (DLT @ 240mg BID); all were reversible with dose interruption 160mg BID selected as RP2D, with dose exploration ongoing at 200 mg BID to further characterize LOXO-292 safety and efficacy AE = adverse event; DLT = dose limiting toxicity; ALT = alanine aminotransferase; AST = aspartate aminotransferase; RP2D = recommended phase 2 dose; Note: Total %s for any given AE may be different than the sum of the individual grades, due to rounding. Patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018.

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Efficacy of LOXO-292 in RET-Altered Cancers 29 40 Maximum change in tumor size (%) RET fusion-positive NSCLC 20 0 # # # * -20 -40 -60 -80 -100 RET fusion-positive pancreatic cancer RET fusion-positive thyroid cancer RET-mutant medullary thyroid cancer Patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018 Note: 7 patients not displayed; 4 due to treatment discontinuation prior to first post-baseline response assessment, 3 due to nonmeasurable disease at baseline (2 stable disease, and 1 complete response). *Complete response; #Unconfirmed response awaiting confirmatory response assessment. NSCLC, non-small cell lung cancer.

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Efficacy of LOXO-292 in RET Fusion-Positive NSCLC (WCLC 2018) 30 ORR (95% CI) 68% (n=26/38) (51–83%) Confirmed ORR* (95% CI) 68% (n=25/37) (50–82%) CR – PR** 26 SD 8 PD 2 NE 2 40 20 0 –20 –40 –60 –80 –100 Best tumor response (%) Prior Chemo Prior IO Prior MKI 20 mg QD 20 mg BID 40 mg BID 60 mg BID 80 mg BID 120 mg BID 160 mg BID 240 mg BID Starting dose All unconfirmed responses reported at ASCO have since been confirmed RECIST 1.1 responses were seen at all starting dose levels, prior to any intrapatient dose escalation, and in 18/26 (69%) responding patients at each patient’s starting dose Activity independent of prior therapy 4/4 confirmed intracranial responses (1 CR, 3 PR) in patients with measurable CNS lesions pending confirmation; * Excludes one patient with unconfirmed PR pending confirmation at time of data cut-off; ** 25 confirmed PR, 1 unconfirmed PR pending confirmation NSCLC patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018.

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Duration of LOXO-292 Treatment in RET Fusion-Positive NSCLC (WCLC 2018) 31 NSCLC patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018. First response Treatment after progression Still on treatment 24/38 (63%) escalated to/treated with 160 mg BID (RP2D) 25/26 (96%) responding patients remain on therapy 24/26 (92%) responses ongoing, 17 responses 6 months Median follow up: 8.5 (0.3–14.1) months, 9.5 (4.4–14.1) months for responding patients Time on treatment (months) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

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Efficacy of LOXO-292 in RET-Mutant MTC and RET Fusion-Positive Thyroid Cancer (ATA 2018) 32 All unconfirmed responses at ASCO have since been confirmed 17/24 (71%) responding patients responded at patient’s starting dose Activity independent of prior therapy 1/1 intracranial response (1 PR, pending confirmation) in RET fusion-positive thyroid patient with measurable CNS lesions RET-mutant MTCa RET fusion-positive thyroid cancerb ORR (95% CI) 59% (17/29) (39–77%) 78% (7/9) (40–97%) Confirmed ORR (95% CI) 56% (15/27)c (35–75%) 78% (7/9) (40–97%) CR 2 – PRd 15 7 SD 8 2 PD 2 – NE 2 – 20 mg QD 20 mg BID 40 mg BID 60 mg BID 80 mg BID 120 mg BID 160 mg BID 240 mg BID Starting dose Best tumor response (%) Prior cabozantinib Prior vandetanib Prior other MKI – 80 – 60 – 40 – 20 0 20 40 – 100 * Prior RAI Prior lenvatinib Prior sorafenib Prior other therapy RET-mutant MTC RET fusion-positive thyroid cancer pending confirmation, complete response. Patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018. a. Includes 2 patients with non-measurable disease (confirmed CR and SD); b. Includes 1 patient with non-measurable disease (SD) c. Excludes two patients with unconfirmed PRs pending confirmation at time of data cut-off; d. RET-mutant MTC includes 13 confirmed PR, 2 unconfirmed PRs pending confirmation; Note: The three patients with non-measurable disease are not shown on the waterfall plots *

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Duration of LOXO-292 in RET-Mutant MTC and RET Fusion-Positive Thyroid Cancer (ATA 2018) 33 1. One patient withdrew consent from study treatment while in response. Patients enrolled as of April 2, 2018. Follow-up as of July 19, 2018. Time on treatment (months) RET-mutant MTC RET fusion-positive thyroid Escalated to/treated with 160 mg BID (RP2D) 21/29 (72%) 7/9 (78%) Responders remain on therapy 16/171 (94%) 7/7 (100%) Responses ongoing 16/171 (94%) 7/7 (100%) Median follow up for all patients 7.6 months (0.4–13.9) 7.6 months (3.7–10.4) Median follow up for responders 8.4 months (4.3–11.5) 8.5 months (6.9–10.4) First response Treatment after progression Still on treatment RET-mutant MTC RET fusion-positive thyroid 0 3 9 12 15 6

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LOXO-292 Next Steps LIBRETTO-001 Phase 2 cohorts currently enrolling at 160 mg BID Regulatory – BTDs received September & October 2018 Based on written meeting minutes from FDA, NDA filing expected in late 2019 utilizing data generated from the ongoing LIBRETTO-001 clinical trial Timeline integrates standard NDA activities which are ongoing and planned, including clinical pharmacology studies, non-clinical studies, and manufacturing BTD indication statements RET Fusion NSCLC: “for the treatment of patients with metastatic RET-fusion-positive non-small cell lung cancer who require systemic therapy and have progressed following platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy” RET Mutant MTC: “for the treatment of patients with RET-mutant medullary thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options” RET Fusion Thyroid Cancer: “for the treatment of patients with advanced RET fusion-positive thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.” Diagnostics Enrolling based on local testing Working with Illumina to clinically validate TST170 as companion diagnostic Next data update is expected to be the registrational dataset, in 2019 34

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35 LOXO-305 (BTK)

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Why Develop a Selective, Non-Covalent BTK Inhibitor? Covalent (irreversible) BTK inhibitors have transformed the treatment of B-cell malignancies (e.g. chronic lymphocytic leukemia, mantle cell lymphoma, Waldenstrom’s macroglobulinemia, marginal zone lymphoma, etc) ibrutinib, acalabrutinib, tirabrutinib, zanubrutinib Chronic therapies taken by 10,000s worldwide, but not curative Next-generation opportunities Resistance C481S mutation at covalent binding site Selectivity reduced off-target adverse events, co-morbidity complications Recent publication of real-world analysis of 616 ibrutinib-treated CLL patients suggests that 50-60% of discontinuations are due to intolerance1 Delivering robust human BTK target coverage without a covalent warhead requires deliberate medicinal chemistry 36 Thesis: Selectivity and reversibility can address BTK acquired resistance and minimize adverse events 1. Mato et al. Haematologica 103(5):874-879. 2018.

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C481S: Emerging, Class-wide Acquired Resistance Covalent BTK inhibitors all bind to BTK cysteine at position 481 A mechanism of acquired resistance has emerged called a C481S mutation that may explain 60-70% of progression events (cysteine mutates to serine)1 Likely to occur across all covalent BTK inhibitors (e.g. ibrutinib1, acalabrutinib2, tirabrutinib, zanubrutinib) Emerging in CLL, MCL, and WM In CLL, median overall survival post-relapse <2 years Non-covalent BTK inhibitors may re-induce a new response and restore disease control by potent binding to BTK without reliance on cysteine at position 481 Testing for C481S is not yet routine, but technically straightforward, utilizing blood, bone marrow, or lymph node tissue 37 1. Woyach et al. JCO 35; 13. 2017. 2. Byrd et al. NEJM 374;4. 2016.

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LOXO-305 is Highly Selective in Cellular Assays 180 Kinases Analyzed 38 BTK TEC

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LOXO-305 Inhibits BTK Autophosphorylation and Signaling Activity in Cells (SOHO 2018) 39 RAMOS RA1 (Burkitt’s lymphoma) BTK phospho-Y223 (Area) (mean ± SD) BTK phospho-Y223 (Area) (mean ± SD) BTK phospho-Y223 (Area) (mean ± SD) LOXO-305 IC50 = 8.8 ± 1.8 nM LOXO-305 IC50 = 3.13 ± 0.6 nM Ibrutinib nM LOXO-305 and ibrutinib effects on BTK autophosphorylation of tyrosine 223 (Y223) and phosphorylation of PLC2 tyrosine 1217 (Y1217). HEK293 cells stably expressing BTK (A and B) and BTK C481S (C and D) were treated for 2 h with LOXO-305 or ibrutinib and analyzed by immunoblot (A and C). B and D: BTK Y223 phosphorylation was normalized to total BTK and IC50 values were calculated using a 4-parameter fit in GraphPad Prism 7.04 software. E and F: Ramos RA1 human Burkitt’s lymphoma cells were treated for 2 h with LOXO-305 or ibrutinib followed by 5 min stimulation with anti-IgM. E: Samples were analyzed by immunoblot for phosphorylation of BTK Y223 and PLC2 Y1217. F: LOXO-305 dose response curve of BTK Y223 phosphorylation in Ramos RA1 cells. BTK Y223 phosphorylation was normalized to total BTK and IC50 values were calculated using a 4-parameter fit in GraphPad Prism 7.04 software A B C D E F 0.0001 0.01 1 100 10000 0 200000 400000 600000 800000 1000000 1200000 1400000 Inhibitor concentration (nM) B T K p h o s p h o - Y 2 2 3 ( A r e a ) ( m e a n ± S D ) LOXO-305 + anti-IgM Ibrutinib + anti-IgM - anti-IgM LOXO-305 IC 50 : 3.13 ± 0.6 nM

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LOXO-305 is Predicted to Achieve High BTK and BTK C481S Target Coverage (SOHO 2018) 40 Time Time Predicted Human Exposure at Steady State (Oral Dosing) Predicted human exposure of LOXO-305 and BTK target coverage. Two planned dose levels of LOXO-305 were modeled using the GastroPlus TM software suite. These illustrate human dose predictions for dose levels planned in the phase 1 dose escalation trial and are not necessarily indicative of the first and second cohorts of the trial. The predicted BTK (wild-type and C481S) target coverage lines were derived from the LOXO-305 inhibition values of autophosphorylation in BTK and BTK C481S HEK293 cells and the plasma protein binding of LOXO-305.

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LOXO-305: Next Steps Phase 1 clinical trial initiation planned for 4Q 2018 Opportunity for patient enrichment in Phase 1 As more patients are treated with irreversible BTK inhibitors, more patients will relapse Expect single agent activity at biologically relevant doses 41

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Upcoming Milestones 42 PROGRAM UPDATE GUIDANCE Larotrectinib (LOXO-101, TRK) FDA NDA PDUFA Date Nov. 26, 2018 Potential EMA approval* 2019 LOXO-195 (TRK) Clinical data update from ongoing Phase 1/2 trial First Half 2019 LOXO-292 (RET) Registrational data 2019 NDA submission Late 2019 LOXO-305 (BTK) Initiate Phase 1 study 4Q 2018 * Per partnership agreement, MAA is handled by Bayer.

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Financials and Capitalization Nasdaq: LOXO Shares Outstanding*: 30.6M basic, 4.2M options ($53.52 weighted avg strike price) Cash, cash equivalents, and investments*: $647.6M Bayer partnership milestones $450M in milestones associated with larotrectinib regulatory approvals and first commercial sale events in certain major markets $275M expected in 2018; $125M expected in 2019 $200M in milestones associated with LOXO-195 regulatory approvals and first commercial sale events in certain major markets $25M milestone upon reaching a certain U.S. net sales threshold $475M in ex-U.S. sales milestones 43 * As of Q3 2018 10-Q

 

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