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: June 3, 2017

(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 x

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. x

Item 7.01 Regulation FD.

On June 3, 2017, Loxo Oncology, Inc. (“Loxo Oncology”) issued two press releases. One press release announced updated clinical data for Loxo Oncology’s ongoing larotrectinib trials as reported by study investigators at the 2017 American Society of Clinical Oncology Annual Meeting (“ASCO”) in Chicago. The second press release announced a clinical proof of concept publication for next-generation TRK inhibitor LOXO-195. A copy of the press releases are furnished as Exhibit 99.1 and 99.2, respectively, to this report and incorporated herein by reference. A copy of the slides presented by the study investigators at ASCO are furnished as Exhibit 99.3 and Exhibit 99.4 to this report and incorporated herein by reference.

On June 4, 2017, Loxo Oncology held an investor conference call. A copy of the slides presented during the investor conference call are furnished as Exhibit 99.5 to this report and incorporated herein by reference.

The information furnished with this report, including Exhibit 99.1, Exhibit 99.2, Exhibit 99.3, Exhibit 99.4 and Exhibit 99.5, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“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 dated June 3, 2017.
99.2	Press release dated June 3, 2017.
99.3	Slides presented by study investigators on June 3, 2017.
99.4	Slides presented by study investigators on June 5, 2017.
99.5	Slides presented by Loxo Oncology on June 4, 2017.

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: June 5, 2017	By:	/s/ Jennifer Burstein
	Name:	Jennifer Burstein
	Title:	Vice President of Finance and principal financial officer

3

EX-99.1

Exhibit 99.1

Loxo Oncology Breakthrough Therapy Larotrectinib Demonstrates 76 Percent Confirmed Objective Response Rate in TRK Fusion Adult and Pediatric Cancers as Presented at the American Society of Clinical Oncology Annual Meeting

— Responses to Selective TRK Inhibitor Observed Across Tumor Types Harboring TRK Fusions —

— 93 Percent of All Responding Patients Remain on Larotrectinib or Received Surgery with Curative Intent —

—Three Clinical Trials Presented Today as Late-Breaker to Form the Basis of Worldwide Regulatory Filings for Potential First-In-Class Therapy Larotrectinib —

— Company to Host Conference Call and Webcast on Sunday, June 4, 2017 at 5:30 p.m. CT —

STAMFORD, Conn., June 3, 2017 — Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, today announced interim clinical data from all three ongoing larotrectinib (LOXO-101) clinical trials in patients whose tumors harbor tropomyosin receptor kinase (TRK) fusions. These data, demonstrating a 76 percent confirmed objective response rate (ORR) across tumor types, are being presented today at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (abstract LBA2501). The larotrectinib pediatric data, included in this presentation, are also being presented in a separate oral presentation on Monday, June 5th (abstract 10510).

“Larotrectinib delivers consistent and durable responses in TRK fusion patients across all ages, regardless of tumor context, and does so with few side effects,” said David Hyman, M.D., the NAVIGATE global principal investigator and chief of the early drug development service at Memorial Sloan Kettering Cancer Center who will present the data at ASCO. “In this way, the larotrectinib TRK fusion story fulfills the promise of precision medicine, where tumor genetics rather than tumor site of origin define the treatment approach. It is now incumbent upon the clinical oncology and pathology communities to examine our testing paradigms, so that TRK fusions and other actionable biomarkers become part of the

standard patient workup.”

The ASCO presentation includes adult and pediatric patients with RECIST-evaluable TRK fusion cancers enrolled across all three larotrectinib clinical trials, and employs an April 14, 2017 data cut-off. These patients will serve as the basis for the larotrectinib New Drug Application (NDA), which the company expects to submit in late 2017 or early 2018 for evaluation by the U.S. Food and Drug Administration (FDA). The primary analysis for the NDA will rely upon central, independent radiology review, which will be performed in the second half of 2017. The company plans to announce these data, which will also include additional patient follow-up, before the end of 2017.

Larotrectinib received Breakthrough Therapy Designation from the FDA in July 2016, “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.”

“The Loxo Oncology team is proud to have contributed to these important data presentations at ASCO,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “We are grateful to the patients, families, and clinical trial teams who help push the boundaries of available care through their participation in clinical trials. We hope that larotrectinib is the first of many new medicines we develop together.”

Key Data Presented at ASCO

The primary efficacy outcome measure for the analysis presented at ASCO is objective response rate (ORR) as measured by RECIST v 1.1. Key secondary endpoints include duration of response (DOR), progression-free survival (PFS) and safety. The data presented at ASCO, summarized below, are based on response assessments as performed by each respective clinical trial site (local, investigator-assessed radiology). A separate response assessment performed by independent radiologists, not yet conducted, will be required to support global regulatory filings.

Consistent with written FDA correspondence, TRK fusion patients enrolled in Loxo Oncology’s Phase 1 adult trial, Phase 2 trial (NAVIGATE), and Phase 1/2 pediatric trial (SCOUT) contributed to the primary efficacy analysis. The data presented are based on the intent to treat (ITT) principle, using the first 55 TRK fusion patients with RECIST-evaluable disease enrolled to the three clinical trials, regardless of prior therapy or tumor tissue diagnostic method.

Forty-three adult and 12 pediatric patients were enrolled, identified by 15 different lab tests. TRK fusion patients carried primary diagnoses of appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, gastrointestinal stromal tumor (GIST), infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. One patient had central nervous system (CNS) metastases at study entry.

	Enrolled Patients with Confirmatory Response Data Available (n=50)	All Enrolled Patients (n=55)*
Objective Response Rate (ORR = PR+CR)	76% (95% CI: 62% — 87%)	78% (95% CI: 65% — 88%)
Partial Response (PR)	64%	65%*
Complete Response (CR)	12%	13%*
Stable Disease	12%	11%
Progressive Disease	12%	11%

* Includes unconfirmed responses with confirmatory scans pending (4 PR, 1 CR). All patients with unconfirmed responses remain in response and ongoing on study.

As shown in the above table, the confirmed ORR is 76 percent in 50 patients for whom follow-up was sufficiently long to include a confirmatory scan. The ORR is 78 percent when an additional 5 patients, recently enrolled, with unconfirmed PR (n=4) and CR (n=1), are included. ORR was generally consistent across tumor types, TRK gene fusions, and various diagnostic tests. In the pediatric setting, larotrectinib showed promising activity in the pre-surgical management of patients with infantile fibrosarcoma, with 3 patients treated to best response, which allowed for subsequent referral to surgery with curative intent.

Median DOR and PFS have not been reached. Ninety-three percent of all responding patients either remain on drug or received surgery with curative intent. Seventy-five percent of all patients enrolled either remain on drug or received surgery with curative intent.

The safety data presented at ASCO encompass the entire larotrectinib safety database in cancer patients (n=125) intended to support an NDA. The most common treatment-emergent adverse events, regardless of relationship to larotrectinib, included fatigue (15% Grade 1, 18% Grade 2, 5% Grade 3), dizziness (22% Grade 1, 4% Grade 2, 2% Grade 3), nausea (20% Grade 1, 5% Grade 2, 2% Grade 3), and anemia (8% Grade 1, 9% Grade 2, 9% Grade 3). Seven (13%) of patients required a dose reduction due to an adverse event. Of note, all patients requiring dose reduction experienced tumor regression (1 CR, 5 PR, 1 SD), which has continued on the reduced dose. Nearly all of the dose reductions were due to infrequent neurocognitive adverse events, likely a result of on-target TRK inhibition in the CNS. No patients discontinued larotrectinib due to an adverse event.

Six patients responded to larotrectinib but subsequently progressed, a pattern referred to as “acquired resistance.” Progression biopsies from five of six patients indicate a consistent mechanism of acquired resistance, namely a solvent front mutation. A solvent front mutation is an amino acid substitution in a kinase that reduces the binding potency of a targeted drug. In the case of NTRK1 and NTRK3, these solvent front amino acid substitutions are denoted as G595R and G623R, respectively. The presence of an acquired resistance mutation in a primary activating oncogene suggests that the involved cancer cell remains dependent on the aberrant signaling pathway that had been successfully drugged previously.  LOXO-195, Loxo Oncology’s next-generation selective TRK inhibitor, was designed to address solvent front and other acquired resistance mutations to potentially induce new responses in TRK fusion dependent cancers with acquired resistance mutations.

About the ASCO Presentations

These data are being presented in two oral presentations at ASCO.

·“The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers.” This includes the integrated database across the three larotrectinib clinical trials and is being presented by Dr. David Hyman, Memorial Sloan Kettering Cancer Center, during the Session entitled, “Developmental Therapeutics — Clinical Pharmacology and Experimental Therapeutics,” from 1:15 — 4:15PM CT on Saturday, June, 3, 2017 (Abstract LBA2501).

·“A pediatric phase 1 study of larotrectinib, a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family.” This focuses specifically on the pediatric Phase 1 clinical trial data, included in the aforementioned data set, and is being presented by Dr. Theodore Laetsch, University of Texas Southwestern Medical Center, during the Session entitled, “Pediatric Oncology II,” from 8:00 — 11:00AM CT on Monday, June, 5, 2017 (Abstract 10510).

The presentations will be available online at http://www.loxooncology.com/asco at the time of their scheduled presentation at ASCO.

Conference Call and Webcast Information

Loxo Oncology will host a conference call and live webcast with slides and Q&A on Sunday, June 4, 2017 at 5:30 p.m. CT to discuss the larotrectinib data. Loxo Oncology management will be joined by the

primary investigators of the larotrectinib clinical development program, Dr. David Hyman and Dr. Alex Drilon of Memorial Sloan Kettering Cancer Center, and Dr. Theodore Laetsch of University of Texas Southwestern Medical Center. To participate in the conference call, please dial (877) 930-8065 (domestic) or (253) 336-8041 (international) and refer to conference ID 14447513. A live webcast of the presentation will be available at http://ir.loxooncology.com/. A replay of the webcast will be available shortly after the conclusion of the call and archived on the company’s website for 90 days following the call.

About Larotrectinib (LOXO-101)

Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 76 percent confirmed objective response rate (ORR), across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

About TRK Fusion Cancer

TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

About Loxo Oncology

Loxo Oncology is a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically 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, thereby 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, statements we make regarding the timing and success of our clinical trials, the potential therapeutic benefits and economic value of our lead product candidate or other product candidates, and timing of

future filings. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q, 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.

###

Contacts for Loxo Oncology, Inc.

Company:
Jacob S. Van Naarden
Chief Business Officer

jake@loxooncology.com

Investors:

Peter Rahmer
The Trout Group, LLC
646-378-2973
prahmer@troutgroup.com

Media:

Dan Budwick

1AB Media

973-271-6085

dan@1abmedia.com

EX-99.2

Exhibit 99.2

Loxo Oncology Announces Clinical Proof of Concept Publication for Next-Generation TRK Inhibitor LOXO-195

STAMFORD, Conn., June 3, 2017 — Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, today announced the online publication of a new research brief in Cancer Discovery outlining the preclinical rationale for LOXO-195 and clinical proof-of-concept data from the first two patients treated. LOXO-195 was developed to treat patients with TRK fusion cancers who become resistant while receiving another TRK inhibitor, such as Loxo Oncology’s larotrectinib.

“This publication highlights the potential for LOXO-195 to extend the period of durable disease control for patients with TRK fusion cancers,” said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. “We believe that today’s ASCO presentation establishes larotrectinib as the clear first choice for patients with TRK fusion cancers.  However, over time, patients will require new treatment options, since oncogene-addicted metastatic cancers ultimately evade targeted therapies. We have been relentless in the development of LOXO-195 so that it could be ready in time for the current larotrectinib clinical trial participants and future patients who depend upon us to realize the full potential of TRK inhibition in the management of advanced cancer.”

LOXO-195 was designed to address anticipated mechanisms of acquired resistance in cancers exposed to a prior TRK inhibitor, including “solvent front” mutations (e.g. NTRK1 G595R, NTRK3 G623R), which are not well-addressed by existing investigational agents. LOXO-195 will be developed as a sequential treatment, to follow larotrectinib or another TRK inhibitor, to extend the total time of benefit from TRK inhibition.

The Cancer Discovery research brief provides early but encouraging evidence that the sequential use of larotrectinib followed by LOXO-195 could extend the total duration of disease control for patients with TRK fusion cancers. An analogous paradigm has already been established for other oncogene-addicted tumors, such as those driven by androgen and estrogen signaling, EGFR mutations and ABL gene fusions. The brief describes the first two patients with TRK fusion cancers who responded to larotrectinib but later relapsed. An adult with colorectal cancer and a child with infantile fibrosarcoma were biopsied at the time of tumor progression and found to have a solvent front TRK mutation in the existing TRK fusion, which explained the diminished activity of larotrectinib. As no other treatment options exist to address TRK fusion solvent front mutations, Loxo Oncology, in collaboration with the U.S. FDA, enabled these patients to access LOXO-195 through emergency use Investigational New Drug applications (INDs). Both patients responded to LOXO-195, with minimal adverse events reported.

A formal LOXO-195 IND was recently cleared by the U.S. FDA, and a Phase 1/2 trial is opening globally.

About LOXO-195

LOXO-195 is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that have acquired resistance to initial TRK therapy such as larotrectinib. Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. Though drugs such as larotrectinib can induce durable responses in these patients, the cancer may eventually begin to grow again. This phenomenon is called “acquired resistance,” in that the cancer has acquired features conferring resistance to the initial therapy that was once effective. Emerging data in the field of TRK inhibition suggest that acquired resistance may emerge due to TRK kinase point mutations,

such as those in the solvent front domain, xDFG domain, or gatekeeper region. LOXO-195 was designed to address these new point mutations and induce a new response in the patient’s cancer. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or email clinicaltrials@loxooncology.com.

About TRK Fusion Cancer

TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.

About Loxo Oncology

Loxo Oncology is a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically 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, thereby 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 availability of funding, timing and success of our clinical trials and the potential therapeutic benefits of our product candidates. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q, 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.

# # #

Contacts for Loxo Oncology, Inc.

Company:

Jacob S. Van Naarden

Chief Business Officer

jake@loxooncology.com

Investors:

Peter Rahmer

The Trout Group, LLC

646-378-2973

prahmer@troutgroup.com

Media:

Dan Budwick

1AB Media

973-271-6085

dan@1abmedia.com

EX-99.3

Exhibit 99.3

The efficacy of larotrectinib (LOXO-101), a selective tropomyosin receptor kinase (TRK) inhibitor, in adult and pediatric TRK fusion cancers Hyman DM,1 Laetsch TW, 2 Kummar S,3 DuBois SG,4 Farago AF,5 Pappo AS,6 Demetri GD,7 El-Deiry WS,8 Lassen UN,9 Dowlati A,10 Brose MS,11 Boni V,12 Turpin B,13 Nagasubramanian R,14 Cruickshank S,15 Cox MC,15 Ku NC,15 Hawkins DS,16 Hong DS,17 Drilon AE1 1Memorial Sloan Kettering Cancer Center, New York, NY; 2University of Texas Southwestern, Dallas, TX; 3Stanford University School of Medicine, Palo Alto, CA; 4Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center, Boston, MA; 5Massachusetts General Hospital, Boston, MA; 6St. Jude Children's Research Hospital, Memphis, TN; 7Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA; 8Fox Chase Cancer Center, Philadelphia, PA; 9Rigshospitalet, Copenhagen, Denmark; 10UH Cleveland Medical Center, Cleveland, OH; 11Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; 12START Madrid CIOCC, Hospital HM Universitario Sanchinarro, Madrid, Spain; 13Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 14Nemour's Children's Hospital, Orlando, FL; 15Loxo Oncology, Inc., San Francisco, CA; 16Seattle Children’s Hospital, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA; 17The University of Texas MD Anderson Cancer Center, Houston, TX Hyman, LBA2501

Role of TRK in normal Neurotrophin family of receptors biology and cancer TRK fusions • • TRKA (NTRK1) Pain, thermoregulation Ligand binding domain (LBD) replaced by 5’ fusion partner Drives overexpression and ligand-independent activation TRKB (NTRK2) Movement, memory, mood, appetite, body weight NTRK1/2/3 Proprioception TRKC (NTRK3) ERK AKT TRK uncommonly expressed in normal tissues or cancer Fusion drives abnormally high expression and activation of TRK kinase domain 2 Hyman, LBA2501 Tyr Tyr Tyr Tyr Tyr Tyr 5’ pa rtner NTRK kina se domain 5’ partner NTRK kinase domain 5’ partner NTRK kinase domain Promoter 5’ partner LBD kinase domain

TRK fusions found in diverse Brain cancers (glioma, GBM, astrocytoma) Salivary (MASC) Thyroid cancer Lung cancer Secretory breast cancer Pancreatic cancer histologies Common cancer with low TRK fusion frequency Rare cancer with high TRK fusion frequency Cholangiocarcinoma GIST Colon Melanoma Gliomas Thyroid cancer Infantile fibrosarcoma Congenital nephroma Spitz nevi Sarcoma (multiple) Sarcoma (multiple) Estimated 1,500–5,000 patients harbor TRK fusion-positive cancers in the United States annually 3 Hyman, LBA2501

Detecting TRK fusions • Several modalities: – DNA & RNA NGS, FISH, IHC Large NTRK introns (compared to ALK, ROS1, RET) make DNA-based detection challenging • • Loxo/Ventana developing Pan-TRK IHC companion diagnostic (CDx) • NGS “universal” CDx tests under FDA review include TRK fusion detection* More info: www.TRKtesting.com *FoundationOne, Oncomine Universal Dx Courtesy of J. Hechtman, Memorial Sloan Kettering 4 Hyman, LBA2501 Pan-TRK IHC detects expression, shared among TRK fusions 200x 40x

Larotrectinib TRKA/B/C • Larotrectinib is the first and only selective pan-TRK inhibitor in clinical development • Highly potent against TRKA, TRKB, TRKC –5–11 nM IC50 in cellular assays Highly selective • • Development timeline – – – March 2015: 1st TRK-fusion patient treated July 2016: breakthrough therapy designation February 2017: pivotal enrollment complete 5 Hyman, LBA2501

Larotrectinib TRK fusion development program • Age >18 years N=55 TRK fusion patients n=12 • Advanced solid tumors Data cut-off: April 14, 2017 6 Hyman, LBA2501 NAVIGATE: adult/adolescent phase II ‘basket’ trial • Age >12 years • TRK fusion positive SCOUT: pediatric phase I/II • Age <21 years • Advanced solid tumors Adult phase I • Advanced solid tumors •TRK fusion status determined by local CLIA (or similarly accredited) laboratories •Primary endpoint – Best objective response rate (ORR) – RECIST v1.1 per investigator assessment • Secondary endpoints – Duration of response (DOR) – Progression-free survival (PFS) – Safety • Dosing – Single-agent larotrectinib, administered predominantly at 100 mg BID continuously – Treatment beyond progression permitted if patient continuing to benefit

Patient demographics 7 Hyman, LBA2501 Characteristic Total (n=55) Gender, n (%) Male29 (53) Female26 (47) Median age (range), years45.0 (0.3–76.0) Age group, n (%) <2 years6 (11) 2–6 years5 (9) 6–15 years1 (2) 15–39 years12 (22) >40 years31 (56) ECOG PS, n (%) 027 (49) 122 (40) 26 (11) No. of prior systemic chemotherapies, n (%) 0–130 (55) 28 (15) >317 (31) CNS metastases, n (%)1 (2)

Diversity of cancers treated - 17 unique types Inflammatory myofibroblastic kidney tumor 2% Salivary gland 22% Breast 2% Infantile Appendix 2% Pancreatic myofibromatosis Peripheral nerve sheath tumor 4% Sarcoma, NOS 4% Myopericytoma 4% 2% 2% Cholangiocarcinoma 4% Infantile fibrosarcoma (IFS) 13% Spindle cell sarcoma 5% GIST 5% Thyroid 9% Melanoma 7% Lung 7% Colon 7% 8 Hyman, LBA2501

Clinical activity of larotrectinib TRK fusion cancers in patients with *Includes unconfirmed responses with confirmatory scans pending (4 PR, 1 CR). All remain in response and ongoing on study. 9 Hyman, LBA2501 Enrolled patients with confirmatory response data available (n=50) All enrolled patients (n=55)* Objective response rate76%78% (95% CI)(62–87%)(65–88%) Partial response64%65%* Complete response12%13%* Stable disease12%11% Progressive disease12%11%

Efficacy of larotrectinib in TRK fusion cancers 93.2 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 Partial response Complete response 64% 12% * # # *Patient had TRK solvent front resistance mutation (NTRK3 G623R) at baseline due to prior therapy; #Pathologic CR Note: One patient not shown here. Patient experienced clinical progression and no post-baseline tumor measurements were recorded. 10 Hyman, LBA2501 Maximum change in tumor size (%) Stable disease12% Progressive disease12% Patients with confirmatory response data available (n=50) Objective response rate (95% CI)76% (62–87%)

Efficacy 93.2 50-.- regardless of age •Adultpatients 40 30-20 - 10 -;-h cu ·u; 5 0 -10 -u---m----u-------;----.Ea .!: -20--30 -40 -50--60 -70--80 -90-cu Cl - ---r--c -;------------c:: (IJ ..r::. <> E ::::1 E ')( (IJ ........-........ .......... -100-.....n....n._.. # # 'Patient had TRK solvent front resistarce mutat1on (NTRK3 G623R) at baseline due to pr1or therapy; l?athologc CR Note One patient not shown here. Patient experienced clinicalprogression and no post-baseline tumor measurements were recorded. 1 11 EDAT: Hyman, LBA2501 Slides are the property of the author. Perm1ss1on required for reuse. PR ESENT #ASC017 17 ASCO ANNUAL MEETING . • Pediatric patients ,...., ......., -------------------------------------------------------------------In - .._.. .._ ._ r-----------.... r--c-----;-..._ ....... .................. .... .... ...... ...._. .........._ .._ ......

Efficacy regardless of tumor type 93.2 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 * Thyroid Colon Melanoma Soft tissue sarcoma Lung GIST Appendix IFS Breast Salivary gland Cholangiocarcinoma Pancreas # # *Patient had TRK solvent front resistance mutation (NTRK3 G623R) at baseline due to prior therapy; #Pathologic CR Note: One patient not shown here. Patient experienced clinical progression and no post-baseline tumor measurements were recorded. 12 Hyman, LBA2501 Maximum change in tumor size (%)

Efficacy regardless of NTRK gene 93.2 50-40 30-• NTRK1 • NTRK2 NTRK3 r-......., 20" ,_ ,_ ---------------------------------------------------------------------i<1) -30 r--------------------u---------E----------:---------------------E-----r-.... ......_ .... .., E ::::1 -40 -50--60 -70--80 -90--100-E ')( (IJ .... .... ............ .... .... # # *Patient had TRK solvent front resistarce mutat1on (NTRK3 G623R) at baseline due to pr1or therapy; l?athologc CR Note One patient not shown here. Patient experienced clinicalprogression and no post-baseline tumor measurements were recorded. 1 13 EDAT: Hyman, LBA2501 Slides are the property of the author. Perm1ss1on required for reuse. PR ESENT #ASC017 17 ASCO ANNUAL MEETING

Efficacy regardless of fusion partner 93.2 NTRK1 NTRK2 NTRK3 LMNA STRN ETV6 TPM3 TPR CTRC PDE4DIP IRF2BP2 SQSTM1 PPL TRIM63 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 TPM4 * # # *Patient had TRK solvent front resistance mutation (NTRK3 G623R) at baseline due to prior therapy; #Pathologic CR Note: One patient not shown here. Patient experienced clinical progression and no post-baseline tumor measurements were recorded. 14 Hyman, LBA2501 Maximum change in tumor size (%)

Duration of larotrectinib therapy progression surgery going esponse 93% of esponding tients and 75% of all patients remain n t atment or underwent surgery with curative ent 0 Median time 3 to response = 1.8 months 6 9 12 15 18 21 24 27 Overall treatment duration (months) No progressions in central nervous system observed 15 Hyman, LBA2501 Treatment after Treatment after Treatment on Time to first r Surgery Pathologic CR int pa r re o

Median duration of response not reached 1.00 91% 0.75 dian follow-up 5.8 months 0.50 0.25 0.00 0 6 12 18 24 30 Months from start of response N=38 3/38 2/17 0/7 0/3 0/0 In patients with confirmed complete or partial response (n=38) 16 Hyman, LBA2501 Probability 79% Me

Median progression-free survival not reached 1.00 75% 0.75 63% Median follow-up 7.7 months 0.50 0.25 0.00 0 6 12 18 24 30 Months from initiation of treatment N=55 12/55 3/27 0/11 0/6 0/1 17 In primary analysis population (n=55) Hyman, LBA2501 Probability

SQSTM1-NTRK1 lung cancer patient Baseline Cycle 4 Courtesy of S. Kummar, Stanford University 18 Hyman, LBA2501 45F NSCLC & paraneoplastic hypertrophic osteoarthropathy Prior therapy: platinum/pemetrexed Larotrectinib ongoing in month 8, resolution of paraneoplastic symptoms

ETV6-NTRK3 infantile fibrosarcoma patient Baseline Cycle 3 19 Courtesy of L. Mascarenhas, CHLA Hyman, LBA2501 2F infantile fibrosarcoma 2 cycles of vincristine/ actinomycin-D/ cyclophosphamide progression leg amputation was only alternative option 4 cycles larotrectinib referred for surgery Pathologic complete response with clear margins No functional deficit post-surgery

ETV6-NTRK3 secretory breast cancer patient Baseline Day 6 Day 20 14F, prior therapy: 4 lines of chemotherapy and repeated resections Treated with larotrectinib under expanded access Courtesy of N. Shukla, Memorial Sloan Kettering 20 Hyman, LBA2501

Adverse events 7 (13%) patients required dose reductions – all maintained tumor regression (1 CR, 5 PR, 1 SD) on reduced dose. No discontinuations for adverse events. Entire safety database (n=125) *TEAEs shown as reported by >15% of patients 21 Hyman, LBA2501 Treatment-related AEs (%) Grade 3 Grade 4 Total 1–18 1–20 2–18 3–10 ––13 1–18 ––12 ––2 4–17 ––6 ––– Treatment-emergent AEs (%)* Grade 1 Grade 2 Grade 3 Grade 4 Total Fatigue15185–38 Dizziness2242–27 Nausea2052–26 Anemia899–26 Vomiting186––24 Increased AST1643–23 Constipation2021–22 Cough182––21 Increased ALT1424–20 Diarrhea1451–20 Dyspnea1062–18

LOXO-195 TRKA G595R to Address TRK Acquired Resistance LOXO-195 Treatment Colorectal TPM3-NTRK1 TRKA G595R NSCLC TPR-NTRK1 TRKA G595R IFS ETV6-NTRK3 TRKC G623R On Treatment Baseline TRKA F589L + Cholangio LMNA-NTRK1 TRK solvent front mutations detected in 5 of 6 patients with acquired resistance. First 2 patients successfully treated with LOXO-195.  Oligometastatic progression, continue on larotrectinib * Gatekeeper mutation 22 Drilon A, Cancer Discovery, Online First (03-JUNE-2017) Hyman, LBA2501 Larotrectinib LOXO-195 * GNAS Q227H Sarcoma TPM3-NTRK1TRKA G595R ColorectalLMNA-NTRK1TRKA G595R Resistance Tumor typeFusionmutation

Larotrectinib conclusions • Consistent and durable antitumor activity in TRK fusion cancers – – – ORR: 76% (12% CRs) 6-month landmark DOR: 91% Minimal side effects for patients • Notable elements of larotrectinib program – – – – – Potentially the first new targeted therapy developed in a tissue type-agnostic manner First new targeted therapy developed simultaneously in adults and pediatrics Rapid path from first patient to last patient enrolled (24 months) New Drug Application (NDA) to be submitted in late 2017 or early 2018 Real-time elucidation of convergent acquired resistance mechanism and treatment with LOXO-195 • For patients with TRK fusion cancer, larotrectinib may offer a potential new standard of care – Routine pan-cancer screening will be important to identify these patients, as well as those with other tumor-agnostic biomarkers (MSI-H) 23 Hyman, LBA2501

Acknowledgements • Patients and their families, many of whom traveled long distances to participate in these studies • National Institutes of Health P30 CA008748 • Marie-Josée and Henry R. Kravis Center for Molecular Oncology 24 Hyman, LBA2501

EX-99.4

Exhibit 99.4

A pediatric phase 1 study of larotrectinib, a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family Laetsch TW, 1 DuBois SG,2 Nagasubramanian R,3 Turpin B,4 Mascarenhas L,5 Federman N,6 Reynolds M,7 Smith S,7 Cruickshank S,7 Cox MC,7 Pappo AS,8 Hawkins DS9 1University of Texas Southwestern/Children’s Health, Dallas, TX; 2Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA; 3Nemours Children's Hospital, Orlando, FL; 4Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 5Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA; 6University of California, Los Angeles, Los Angeles, CA; 7Loxo Oncology, Inc., South San Francisco, CA; 8St. Jude Children's Research Hospital, Memphis, TN; 9Seattle Children’s Hospital, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA Laetsch, 10510

Role of TRK in normal Neurotrophin family of receptors biology and cancer TRK fusions • • TRKA (NTRK1) Pain, thermoregulation Ligand binding domain (LBD) replaced by 5’ fusion partner Drives overexpression and ligand-independent activation TRKB (NTRK2) Movement, memory, mood, appetite, body weight NTRK1/2/3 Proprioception TRKC (NTRK3) ERK AKT TRK uncommonly expressed in normal tissues or cancer Fusion drives abnormally high expression and activation of TRK kinase domain 2 Laetsch, 10510 Tyr Tyr Tyr Tyr Tyr Tyr 5’ pa rtner NTRK kina se domain 5’ partner NTRK kinase domain 5’ partner NTRK kinase domain Promoter 5’ partner LBD kinase domain

Pediatric cancers and TRK Gliomas fusions Rare neoplasm with high TRK fusion frequency Thyroid cancer Secretory breast carcinoma Infantile fibrosarcoma Spitz nevi Congenital mesoblastic nephroma Various sarcomas 3 Laetsch, 10510

Larotrectinib (LOXO-101) TRKA/B/C • Larotrectinib is the first and only selective pan-TRK inhibitor in clinical development • Highly potent against TRKA, TRKB, TRKC (5–11 nM IC50 in cellular assays) Highly selective • • Responses seen in adult patients with TRK fusions • Recommended phase 2 dose in adults is 100 mg BID continuously • Liquid formulation for pediatric patients 4 Laetsch, 10510

Pediatric phase I trial design (SCOUT) n=17 TRK fusion patients n=7 non-fusion patients Data cut-off: April 14, 2017 5 Laetsch, 10510 Eligibility • 1 month – 21 years of age • Relapsed/refractory solid tumor (including CNS) or locally advanced IFS • Evaluable or measurable disease by RECIST v1.1 • Karnofsky/Lansky status >50 • Adequate organ function •Objectives – Safety, including dose-limiting toxicities (DLTs) – Pharmacokinetics – Maximum tolerated dose (MTD) – Antitumor activity •Modified rolling 6 design – Patients with TRK fusion continue to enroll to current dose level during DLT evaluation •Intrapatient dose escalation allowed – Target AUC0–24 >50% of adults at RP2D • TRK fusion status determined by local CLIA (or similarly accredited) laboratories

Patient and disease characteristics 6 Laetsch, 10510 Characteristic Total (N=24) Age group, n (%) <1 year 1–2 years 2–12 years >12 years 5 (21) 2 (8) 10 (42) 7 (29) Median age (range), years 4.5 (0.1–18.0) Female, n (%) 12 (50) Extent of disease at study enrollment, n (%) Locally advanced Metastatic 14 (58) 10 (42) No. of prior systemic therapies, n (%) 0 1 >2 7 (29) 6 (25) 11 (46)

Range of histologies treated 7 Laetsch, 10510 Cancer types, n (%) TRK fusion (n=17) Non-TRK fusion (n=7) Total (N=24) Infantile fibrosarcoma (IFS) 8 (47) 0 8 (33) Soft tissue sarcoma, various 7 (41) 0 7 (29) Primary CNS 0 5 (71) 5 (21) Thyroid 2 (12) 0 2 (8) Neuroblastoma 0 1 (14) 1 (4) Osteosarcoma 0 1 (14) 1 (4)

Dose escalation 100 mg/m2 BID No DLTs No DLTs *Adult equivalent doses by SimCyp modeling 8 Laetsch, 10510 Dose level 2 150 mg BID AED* (n=11) Dose level 1 (starting) 100 mg BID AED* (n=4) No DLTs Interim PK analysis Protocol modification to only BSA-based dosing Dose level 3 max 100 mg (n=9) Recommended Phase 2 Dose 100 mg/m2 BID max 100 mg

Pharmacokinetics Concentration-time AUC0–24 in patients treated with 80–125 mg/m2 BID 1000 20000 n=6 n=9* 15000 100 n=29 n=5 10000 Adults (100 mg BID, n=29) Pediatric (solution formulation) 10 5000 (100 mg/m2, max 100 mg, BID, n=6) Pediatric (capsule formulation) (100 mg/m2, max 100 mg, BID, n=3) 1 0 0 3 6 Time (hours) 9 12 <2 (99 mg/m2) 2–11 (98 mg/m2) 12–18 (96 mg/m2) Adult (100 mg) Age (years) and mean BID dose *One patient included in both <2 and 2–11 year categories (due to aging while on study) 9 Laetsch, 10510 Larotrectinib in plasma (ng/mL) Estimated plasma AUC0–24 (ng*h/mL)

Treatment-emergent AEs related to study drug* *In >10% of patients 10 Laetsch, 10510 Total (n=24) Gr 1 Gr 2 Gr 3 Gr 4 Total 17%–4%–21% 8%4%4%–17% 33%4%––38% 13%8%––21% 13%4%––17% 13%4%––17% 21%4%4%–29% 21%–––21% 17%–––17% 13%–––13% 8%4%––13% 100 mg/m2 (n=9) Gr 1 Gr 2 Gr 3 Gr 4 Total Nausea33%–11%–44% Neutropenia22%–11%–33% Increased AST11%11%––22% Vomiting11%11%––22% Anemia22%–––22% Constipation22%–––22% Increased ALT––11%–11% Leukopenia11%–––11% Hypoalbuminemia11%–––11% Blood creatinine increased11%–––11% Fatigue11%–––11%

High response Non-TRK fusion rate in children with TRK fusion TRK fusions 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 # # Note: 3 Non-NTRK fusion patients not shown due to clinical disease progression without post-baseline tumor measurements. 4 TRK fusion patients not shown due to having non-measurable disease (n=2) or no disease assessments yet/continuing treatment (n=2). #Pathologic CR 11 Laetsch, 10510 Maximum change in tumor size (%) 91.9

Efficacy regardless Non-TRK fusion of tumor type TRK fusion 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 # # Note: 3 Non-NTRK fusion patients not shown due to clinical disease progression without post-baseline tumor measurements. 4 TRK fusion patients not shown due to having non-measurable disease (n=2) or no disease assessments yet/continuing treatment (n=2). #Pathologic CR 12 Laetsch, 10510 Maximum change in tumor size (%) 91.9 IFS Soft tissue sarcoma

Efficacy regardless Non-TRK fusion of TRK gene TRK fusion 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 # # Note: 3 Non-NTRK fusion patients not shown due to clinical disease progression without post-baseline tumor measurements. 4 TRK fusion patients not shown due to having non-measurable disease (n=2) or no disease assessments yet/continuing treatment (n=2). #Pathologic CR 13 Laetsch, 10510 Maximum change in tumor size (%) 91.9 None NTRK1 NTRK2 NTRK3

Efficacy regardless Non-TRK fusion of fusion partner TRK fusion 50 40 30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 # # Note: 3 Non-NTRK fusion patients not shown due to clinical disease progression without post-baseline tumor measurements. 4 TRK fusion patients not shown due to having non-measurable disease (n=2) or no disease assessments yet/continuing treatment (n=2). #Pathologic CR 14 Laetsch, 10510 Maximum change in tumor size (%) 91.9 None NTRK1UnknownTPM3PDE4DIPSQSTM1 NTRK2STRN NTRK3ETV6

Clinical activity of larotrectinib *4 patients not evaluable due to having non-measurable disease (n=2) or no disease assessments yet/continuing treatment (n=2) **Includes unconfirmed responses with confirmatory scans pending (1 PR, 1 CR). Both remain in response and ongoing on study. 15 Laetsch, 10510 TRK fusions (n=17)* Non-fusions Confirmatory response data available (n=11) All patients (n=13) All patients (n=7) Objective response rate (95% CI) 91% (59–100%) 92%** (64–100%) 0 Partial response 64% 62%** 0 Complete response 27% 31%** 0 Stable disease 9% 8% 0 Progressive disease 0 0 100%

Responses occur early and are durable * * Treatment after surgery Treatment ongoing Pathologic CR Post-surgery observation Time to first response #Only patient with TRK fusion to develop PD Confirmed TRKC G623R solvent front resistance mutation Patient re-responded to LOXO-195+ 0 3 6 9 12 15 Overall treatment duration (months) *Patients had non-measurable disease at baseline 16 +Drilon A, Cancer Discovery, Online First (03-JUNE-2017) Laetsch, 10510 Non-TRK fusion TRK fusion #

Rapid response in infant with ETV6-NTRK3 infantile fibrosarcoma (IFS) Baseline Baseline After four doses Before Cycle 3 Courtesy of N. Federman, UCLA 17 Laetsch, 10510 31 do infant with IFS of the scalp Rapid recurrence following surgical resection Marked clinical improvement after four doses of larotrectinib CR after 2 cycles of larotrectinib Remains on therapy after 2 cycles

Rapid and durable response in patient with metastatic STRN-NTRK2 fusion sarcoma Baseline Before Cycle 2 18 Laetsch, 10510 11 yo girl with retroperitoneal undifferentiated sarcoma harboring STRN-NTRK2 fusion Refractory to vincristine/ doxorubicin/cyclophosphamide, ifosfamide/etoposide, sorafenib, and vincristine/irinotecan PR after 1 cycle of larotrectinib with rapid clinical improvement Remains in response after 13 cycles

ETV6-NTRK3 infantile fibrosarcoma patient Baseline Cycle 3 19 Courtesy of L. Mascarenhas, CHLA Laetsch, 10510 2 yo girl with infantile fibrosarcoma 2 cycles of vincristine/ actinomycin-D/ cyclophosphamide progression leg amputation was only alternative option 4 cycles larotrectinib referred for surgery Pathologic complete response with clear margins No functional deficit post-surgery

Larotrectinib is active and well-tolerated in children with TRK fusion cancers • Larotrectinib demonstrated a favorable tolerability profile and histology-independent activity in pediatric patients harboring TRK fusions Recommended phase 2 dose in children: 100 mg/m2 BID continuously, cap 100 mg/dose • – – – No DLTs at any dose level Similar exposure to adults at RP2D Highly active • Phase 2 portion of trial is enrolling globally (Abstract TPS10577) – – Infantile fibrosarcoma Other CNS and extracranial TRK fusion solid cancers 20 Laetsch, 10510

Acknowledgements The authors would like to thank • Patients and their families • Research staff Funded by Loxo Oncology, Inc 21 Laetsch, 10510

EX-99.5

Exhibit 99.5

2017 ASCO Conference Call June 4, 2017 1

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 lead product candidate and second generation product candidate, potential growth opportunities, the timing or success of commercialization, 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 on larotrectinib is derived from the presentation made at the 2017 ASCO Annual Meeting by Dr. Hyman, an independent third-party investigator. 2

Pipeline of Highly Selective Drug Candidates for Genetically Defined Cancers 3 Program Indication Stage of Development Eligible US patients/yr1 Preclinical Phase 1 Phase 2 Marketed Key Milestones Larotrectinib (LOXO-101) TRK fusion cancers Will form the basis of NDA expected to be filed in late 2017 / early 2018 1,500-5,000 Phase 2 Basket Trial “NAVIGATE” Pediatric Phase 1/2 Trial “SCOUT” Adult Phase 1 Trial LOXO-195 Next-generation TRK inhibitor for potential acquired resistance Clinical proof-of-concept recently published Phase 1 starting now 1,500-5,000 LOXO-292 Cancers with RET fusions and RET mutations Phase 1 ongoing Potential clinical data by YE 2017 ~5,000 FGFR2/3 Cancers with FGFR2/3 alterations Lead optimization ongoing 1 Estimated number of late-line eligible patients per year in U.S.

Agenda Review of larotrectinib data presented at ASCO Dr. David Hyman, MSKCC Dr. Alex Drilon, MSKCC Dr. Theodore Laetsch, UT Southwestern Ongoing larotrectinib development activities LOXO-195 LOXO-292 Upcoming milestones / Q&A 4

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Path to Regulatory Filings Clinical Independent radiology review to be conducted 2H 2017 NDA filing will utilize a later data cut-off date relative to ASCO data Trials continue to enroll as mechanism of expanded access CMC scale-up and stability testing ongoing Dictates the expiration date of the commercial product Long-term toxicology ongoing Clinical pharmacology studies ongoing Drug-drug interactions Food effect ADME 23 – NDA submission expected in late 2017 or early 2018 – – MAA submission expected in 2018 –

Larotrectinib Diagnostics Strategy Multiple diagnostic relationships are likely Focused on immunohistochemistry (IHC) and next-generation sequencing (NGS) IHC Collaboration announced with Roche Ventana Loxo/Ventana are creating pan-TRK test 8,500+ installed base of Ventana instruments worldwide NGS Multiple players in an evolving space Keys for Loxo: (1) TRK fusion panel inclusion, (2) FDA path, (3) Payor traction 24

LOXO-195 25

LOXO-195: Structurally Distinct, Similarly Selective 26 LOXO-195 Larotrectinib TRKB TRKB TRKA TRKA

LOXO-195 Clinical Development Clinical proof-of-concept established in Cancer Discovery publication First 2 emergency use patients with PRs 1 additional emergency use patient (unpublished) with limited duration of treatment amidst clinical deterioration 3 remaining larotrectinib RECIST progressions: 2 patients remain on larotrectinib post-progression, 1 patient with clinical deterioration too rapid for LOXO-195 initiation IND cleared by FDA Phase 1/2 trial startup in process Co-locate at high enrolling larotrectinib sites Co-locate at other sites with TRK fusion patients Plan to address patients with TRK fusion cancers harboring solvent front mutations, xDFG mutations, and gatekeeper mutations 27

LOXO-292 (RET) 28

LOXO-292 Phase 1 Trial Design 29 Advanced RET-altered solid tumor Any prior TKIs that inhibit RET ~ 30 patients MTD/ recommended expansion dose 5. Advanced RET-altered solid tumor, any of: Disease not measurable Other RET-altered tumors RET mutation-neg. MTC Any prior TKIs that inhibit RET ~ 15 patients 1. Advanced RET-fusion NSCLC 1 Prior TKI that inhibit RET ~ 15 patients 2. Advanced RET-fusion NSCLC No prior TKI that inhibits RET ~ 15 patients 3. Advanced RET-mutant MTC 1 prior TKI that inhibit RET ~ 15 patients 4. Advanced RET-mutant MTC No prior TKI that inhibits RET ~ 15 patients Target exposure Advanced solid tumor NSCLC = Non-small cell lung cancer MTC = Medullary thyroid cancer Dose Escalation Expansion Cohorts

LOXO-292 Clinical Development First patient enrolled in Phase 1 clinical trial in May 2017 Early human pharmacokinetic data is in line with preclinical predictions Opportunity for patient enrichment in Phase 1 Growing target awareness Detection technology is relatively straightforward Expect single agent activity at biologically relevant doses Potential for initial clinical data by YE 2017 30

Milestones and Capitalization 31 FINANCIAL* NASDAQ: LOXO Shares Outstanding*: 26.2M basic, 3.0M options ($17.63 weighted avg strike price) Cash, cash equivalents, and investments*: $244.3M * As of Q1 2017 10-Q PROGRAM UPDATE DEC 2016 GUIDANCE STATUS Larotrectinib (LOXO-101, TRK) Complete enrollment for primary efficacy analysis dataset Early 2017 Present Phase 1/2 pediatric clinical data Mid-2017 Present interim data for integrated TRK fusion NDA database (local radiology) -- Announce final data for integrated TRK fusion NDA database (central radiology) 2H 2017 On plan Submit NDA with US FDA Late 2017 / Early 2018 On plan LOXO-195 (TRK) Initiate Phase 1 study Mid-2017 (IND clear) Assuming availability of appropriate patients, potential for initial clinical data By Year End 2017 LOXO-292 (RET) Initiate Phase 1 study Early 2017 Potential for initial clinical data By Year End 2017 On plan

Q&A 32