8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (date of earliest event reported): February 28, 2018

Heat Biologics, Inc.

(Exact name of registrant as specified in charter)

Delaware

(State or other jurisdiction of incorporation)

001-35994	26-2844103
(Commission File Number)	(IRS Employer Identification No.)

801 Capitola Drive

Durham, NC 27713

(Address of principal executive offices and zip code)

(919) 240-7133

(Registrant’s telephone number including area code)

N/A

(Former Name and Former Address)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of registrant under any of the following provisions:

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

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

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

¨ 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 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 þ

If an emerging growth company, indicate by checkmark 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.þ 

Item 8.01. Other Events

On February 28, 2018, Heat Biologics, Inc. (the “Company”) issued a press release announcing interim results from its Phase 2 study investigating HS-110 in combination with the Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo®), in patients with non-small cell lung cancer (NSCLC) whose cancers have progressed after treatment with one or more lines of therapy.

Among the 35 patients in the Intent-to-Treat (“ITT”) population, 6 patients (17%) achieved a partial response and 14 patients (40%) achieved disease control. Evaluable ITT patients (those who underwent at least one follow-up scan regardless of treatment duration) demonstrated overall response and disease control rates of 26% and 67%, respectively. Overall responses appeared durable and long lasting. The survival data are still maturing, and median overall survival has not yet been reached. The combination of HS-110 and nivolumab was well tolerated, with no additional toxicities compared to what has been observed with single agent checkpoint inhibitors.

As predefined in the clinical protocol, patient subgroups were evaluated for levels of tumor infiltrating lymphocytes (“TIL”) and for PD-L1 checkpoint protein expression on tumor cells. Four of 9 “cold tumor” patients with low TIL levels (<10%) at baseline had partial responses. HS-110 also showed a durable effect in patients with low levels of PD-L1, with 3 of 9 patients responding. Both of these patient populations respond poorly to checkpoint inhibitors.

A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The Company is also hosting an analyst and investor event on February 28, 2018 to present the interim Phase 2 results. In connection with this analyst and investor event, the Company intends to discuss the slide presentation attached as Exhibit 99.2 to this Current Report on Form 8-K, which is incorporated herein by reference.

The press release attached as Exhibit 99.1 and the slide presentation attached as Exhibit 99.2 to this Current Report on Form 8-K include “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained in the press release or the slide presentation are “forward-looking” rather than historical.

The Company undertakes no duty or obligation to update or revise information included in this Current Report on Form 8-K or the related Exhibits 99.1 or 99.2.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Press Release dated February 28, 2018
99.2	Heat Biologics, Inc. presentation dated February 28, 2018

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.

Dated:  February 28, 2018	HEAT BIOLOGICS, INC.
	By:	/s/ Jeff Wolf
	Name:	Jeff Wolf
	Title:	Chairman, President and Chief Executive Officer

EXHIBIT INDEX

Exhibit No.	Description
99.1	Press Release dated February 28, 2018
99.2	Heat Biologics, Inc. presentation dated February 28, 2018

EX-99.1

EXHIBIT 99.1

Heat Biologics Announces Positive Interim Data from its Phase 2 Clinical Trial of

HS-110 and Nivolumab in Non-Small Cell Lung Cancer (NSCLC)

·

Tumor shrinkage and disease control demonstrated in a majority of evaluable patients

·

HS-110 + nivolumab combination showed durable responses in difficult-to-treat low TIL patients and low PD-L1 patients, who respond poorly to checkpoint inhibitors

·

Data consistent with HS-110 mechanism of action

·

Live Webcast at 8am Eastern Time today

DURHAM, NC – February 28, 2018 – Heat Biologics, Inc. (Nasdaq: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, today announced interim results from its Phase 2 study investigating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo®), in patients with advanced non-small cell lung cancer (NSCLC) whose cancers have progressed after treatment with one or more lines of therapy.

Among the 35 patients in the Intent-to-Treat (“ITT”) population, 6 patients (17%) achieved a partial response and 14 patients (40%) achieved disease control.  Evaluable ITT patients (those who underwent at least one follow-up scan regardless of treatment duration) demonstrated overall response and disease control rates of 26% and 67%, respectively.  Overall responses appeared durable and long lasting. The survival data are still maturing, and median overall survival has not yet been reached. The combination of HS-110 and nivolumab was well tolerated, with no additional toxicities compared to what has been observed with single agent checkpoint inhibitors.

As predefined in the clinical protocol, patient subgroups were evaluated for levels of tumor infiltrating lymphocytes (“TIL”) and for PD-L1 checkpoint protein expression on tumor cells.  Four of 9 “cold tumor” patients with low TIL levels (<10%) at baseline had partial responses. HS-110 also showed a durable effect in patients with low levels of PD-L1, with 3 of 9 patients responding. Both of these patient populations respond poorly to checkpoint inhibitors.

George Peoples, M.D., Chief Medical Officer, stated, “The results from this combination trial with HS-110 and nivolumab are very promising, demonstrating durable responses in those patients with low levels of TIL and PD-L1. These patients represent the most difficult-to-treat patient groups and comprise the majority of the NSCLC population.”

“We look forward to continuing patient enrollment to better define the optimal NSCLC population and inform the design of a pivotal trial,” commented Jeff Wolf, Chairman and CEO.  “These data are consistent with the mechanism of action of our T-cell Activation Platform that promotes a robust T-cell immune response, an important component of an effective immunotherapy combination against cancer.”

DURGA Trial Design

The ongoing DURGA trial is a single arm multicenter trial that was designed to evaluate the combination of HS-110 and nivolumab in patients with NSCLC. Patients with advanced and previously treated NSCLC were treated with weekly HS-110 for 18 weeks and nivolumab 3 mg/kg every 2 weeks until disease progression or death.   The primary endpoints are 1) safety and tolerability, and 2) objective response rate as defined by RECIST 1.1 criteria.  Secondary endpoints include disease control rate, duration of response, peripheral blood immune response, progression-free survival and overall survival.

Live Webcast with Slides

The interim data from the DURGA trial will be presented at an analyst event, taking place at 8am Eastern Time, today, Wednesday February 28th.  To register and watch a live webcast of the event, visit http://lifesci.rampard.com/20180228.

About Heat Biologics, Inc.

Heat Biologics is a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer by inducing CD8+ “Killer” T-cells. Our T-cell Activation Platform (TCAP) produces therapies designed to turn “cold” tumors “hot,” and be administered in combination with checkpoint inhibitor therapies and other immuno-modulators to increase their effectiveness. We are currently enrolling patients in our Phase 2 clinical trial for non-small cell lung cancer, in combination with Bristol-Myers Squibb’s nivolumab (Opdivo®). Pelican Therapeutics, a subsidiary of Heat, is focused on the development of co-stimulatory monoclonal antibody and fusion protein-based therapies designed to activate the immune system. We also have numerous pre-clinical programs at various stages of development. For more information, please visit www.heatbio.com.

Forward Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 on our current expectations and projections about future events. In some cases, forward-looking statements can be identified by terminology such as “may,” “should,” “potential,” “continue,” “expects,” “anticipates,” “intends,” “plans,” “believes,” “estimates,” and similar expressions. These statements are based upon current beliefs, expectations and assumptions and include statements regarding our continued enrollment of patients in this trial, the future pivotal trial and the potential benefits of our products.  These statements are based on management’s expectations and assumptions as of the date of this press release and are subject to a number of risks and uncertainties, many of which are difficult to predict that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements, including the ability of Heat’s ImPACT therapy to perform as designed, to demonstrate safety and efficacy, as well as results that are consistent with results from the interim data and prior results, the ability to enroll patients and complete the clinical trials on time and achieve desired results and benefits, Heat’s ability to obtain regulatory approvals for commercialization of product candidates or to comply with ongoing regulatory requirements, regulatory limitations relating to Heat’s  ability to promote or commercialize its product candidates for specific indications, acceptance of its product candidates in the marketplace and the successful development, marketing or sale of products, Heat’s ability to maintain its license agreements, the continued maintenance and growth of its patent estate, its ability to establish and maintain collaborations, its ability to obtain or maintain the capital or grants necessary to fund its research and development activities, and its ability to retain its key scientists or management personnel, its ability to successfully integrate Pelican, and the other factors described in Heat’s most recent annual report on Form 10-K and other filings with the SEC.  The information in this release is provided only as of the date of this release and the company undertakes no obligation to update any forward-looking statements contained in this release based on new information, future events, or otherwise, except as required by law.

Contact

Media and Investor Inquiries

Melissa Conger

Heat Biologics

+1 919 289 4017

mconger@heatbio.com

EX-99.2

EXHIBIT 99.2

   1  Heat Biologics  Analyst and Investor DayFebruary 28, 2018 

 Forward Looking Statements  This presentation includes statements that are, or may be deemed, ‘‘forward-looking statements’’ within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. In some cases, these forward-looking statements can be identified by the use of forward-looking terminology, including the terms “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately” or, in each case, their negative or other variations thereon or comparable terminology, although not all forward-looking statements contain these words. They appear in a number of places throughout this presentation and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, future trial results being consistent with interim results, our ongoing and planned discovery and development of drugs targeting cancer, the strength and breadth of our intellectual property, our ongoing and planned preclinical studies and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates, our ability to partner our product development, the degree of clinical utility of our products, particularly in specific patient populations, expectations regarding clinical trial data, our results of operations, financial condition, liquidity, prospects, growth and strategies, the length of time that we will be able to continue to fund our operating expenses and capital expenditures, our expected financing needs and sources of financing, the industry in which we operate and the trends that may affect the industry or us.  By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and healthcare, regulatory and scientific developments and depend on the economic circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. Although we believe that we have a reasonable basis for each forward-looking statement contained in this presentation, we caution you that forward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this presentation as a result of, among other factors, the factors referenced in the “Risk Factors” section of our most recent Annual Report on Form 10-K and our quarterly report on Form 10-Q for the subsequent quarters (collectively, our “SEC Filings”). In addition, even if our results of operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-looking statements contained in this presentation, they may not be predictive of results or developments in future periods. Any forward-looking statements that we make in this presentation speak only as of the date of such statement, and we undertake no obligation to update such statements to reflect events or circumstances after the date of this presentation, except as required by law.You should read carefully the factors described in the “Risk Factors” sections of our SEC Filings to better understand the risks and uncertainties inherent in our business.  

 Roger B. Cohen  Professor of MedicineUniversity of PennsylvaniaAssociate Director Clinical Research Abramson Cancer CenterChief Clinical Research Officer Abramson Cancer CenterCo-Director, Head and Neck Cancer Research Center 

 Therapy for Advanced Lung Cancer  There have been some modest gains since 1980   Immunotherapy    Are we doing better with immunotherapy?  Targeted Therapies 

                     Cancer-Immunity Cycle  Chen DS, Mellman I. Immunity. 2013;39:1-10.                                          Release of cancer cell antigens(cancer cell death)  1    Cancer antigen presentation(dendritic cells/APCs)  2    Priming and activation(APCs & T cells)  3    Trafficking of T cells to tumors (CTLs)  4    Infiltration of T cells into tumors(CTLs, endothelial cells)  5    Recognition of cancer cells by T cells(CTLs, cancer cells)  6    Killing of cancer cells(Immune and cancer cells)  7  Lymphnode  tumor  Bloodvessel                                                        APCs = antigen-presenting cells; CTLs = cytotoxic T lymphocytes.  PD-1, PD-L1 antibodies 

 Immune Checkpoints   Immune checkpoints are normal ‘brakes’ on the activity of the immune system; checkpoint proteins turn off activated T cells when they are no longer neededImmune checkpoints have been ‘hijacked’ by the cancer to evade the immune systemCheckpoint Inhibitors  remove the checkpoint and “take the brakes off the immune system”Now the immune system can ‘see’ the tumor and kill it   

 1st Line NSCLC Treatment Landscape  Incurable NSCLC (adenocarcinoma) without activating EGFR, ALK, etc. mutations:If PD-L1 is ≥ 50%, consider Keytruda as monotherapyIf PD-L1 <50%, consider Keytruda in combination with chemotherapyPlatinum doublet chemotherapyIncurable NSCLC (squamous cell):If PD-L1 is ≥ 50%, consider Keytruda as monotherapyIf PD-L1 <50%, platinum doublet chemotherapySoon, many patients will get a checkpoint inhibitor in the first line of therapy 

 2nd Line NSCLC Treatment Landscape  Adenocarcinoma: chemotherapy (taxanes) or checkpoint inhibitor if not given previouslySquamous Cell: chemotherapy (taxanes) or checkpoint inhibitor (Keytruda, Opdivo, Tecentriq) if not given previouslyWhat if the patient already received a checkpoint inhibitor and wants more immunotherapy?They will need a ‘rescue’ strategy: a checkpoint inhibitor “plus something to make the checkpoint inhibitor work or work again”Something = Radiation (“RadVax”)Addition of a 2nd immune modulating drug: IDO inhibitor, IFNγ, or antibodies against CTLA-4, OX40, B7H3, CSFR1, LAG-3, TIGIT, TIM-3, etc.A vaccine (ex: HS-110) that induces CD8+ T cells to infiltrate the tumors 

 The Big Challenge:Most patients with NSCLC don’t respond to checkpoint inhibition 

 Even the “ideal” pts (PD-L1 ≥ 50%) don’t all respond to checkpoint inhibitors  Reck M et al. N Engl J Med 2016;375:1823-1833 

 Considerable Unmet Need in All Lines of Therapy   In the PDL-1 intermediate (1-50%) patients the response rate is lower: ~20-25% In the PDL-1 negative (<1%) patients the response rates are < 10%And patients who do respond are not curedThey eventually get worse and die from NSCLCReasons for failure of checkpoint inhibition likely include:There are no T-cells in the tumor (the tumors are ‘cold’)There are other white blood cells in the tumors that block the T-cells from doing their jobThe cancer is using checkpoints other than PD-1/PD-L1The cancer substitutes new checkpoints when we block PD-1/ PD-L1Unknown mechanisms of immune evasion 

 Immunotherapy Combinations  Improving response rates and response duration will require IO combinations Existing combinations, such as Opdivo-Yervoy are significantly more toxic than Opdivo monotherapyImmune-related toxicities include pneumonitis, colitis, rashes, hepatitis, nephritis, encephalitis and othersAdditive immune therapies that don’t add significant toxicity are needed  Larkin et al, N Engl J Med 2015; 373:23-34 

 Cancer Immunity Cycle (continued)    Infiltration of T cells into tumorsLFA1/1CAM1SelectinsVEGFEndothelin B receptor  5    Trafficking ofT cells to tumors  4  CX3CL1CXCL9CXCL10CCL5    Recognition of cancer cells by T cellsT cell receptorReduced pMHC on cancer cells  6    Killing of cancer cells IFN-γT cell granule content  7  PD-L1/PD-1PD-L1/B7.1IDOTGF-β  BTLAVISTALAG3Arginase  MICA/MICBB7-H4TIM3/phospholipids    Release of cancer cell antigensImmunogenic cell deathTolerogenic cell death  1    n Stimulatory factorsn Inhibitors    Cancer antigen presentationTNF-aIL-1IFN-aCD40L/CD40CDNATPHMGB1TLRIL-10IL-4IL-13  2    Priming & activationCD28/B7.1CD137/CD137LOX40/OX40LCD27/CD70HVEMGITRIL-2IL-12CTLA-4/B7.1PD-L1/PD-1PD-L1/B7.1 prostaglandins  3                                                            Lymphnode  tumor  Bloodvessel                                                        Chen DS, Mellman I. Immunity. 2013;39:1-10.  HS-110  HS-110 

 14  What might a therapeutic vaccine like HS-110 do?Generate CD8+ cells (TILs) that penetrate tumors and make them “hot”  CD8+ (TIL+) patients may respond to anti-PD-(L)1  CD8- (TIL-) patients may not respond to anti-PD-(L)1  Teng et al., 2015 Can ResGettinger et al., 2015 JCO  Hypothesis  Combining Therapeutic Vaccines with Checkpoint Inhibitors    Convert TIL- tumors to TIL+ 

                 Baseline  Week 10  Biopsies from the DURGA Trial:TIL Infiltration Associated with Clinical Response                  Patient 1:Partial Response at Week 18  High CD8+ TIL (>10%)                  Patient 2:Partial Response at Week 9  High CD8+ TIL (>10%)*      Patient 3:Partial Response at Week 18  Low CD8+ TIL (<10%)  High CD8+ TIL (>10%)             

 Previous lung cancer vaccines were not designed to elicit a robust CD8+ T-cell response 

 17  Introducing gp96- The Immune System’s “Swiss Army Knife”*  *Schild, H. & Rammensee, H. Gp-96 – The Immune System’s Swiss Army Knife. Nature Immunology 2, 100-101 (2000)  A Natural “Molecular Warning System”  Gp96 “chaperones” newly-created proteins to the cell membrane where they are released and embeddedGp96 + its ferried protein are naturally released only via necrosisExposure of gp96 outside the cell activates an immune response to the antigen it is carrying Enables MHC I antigen cross-presentation specifically to CD8+ T-cellsActivates a cytotoxic T-cell response to the cargo antigenGp96 among the most powerful immune adjuvantsGp96 is the only adjuvant that generates exclusively CD8+ (“killer”) T-cells 

 Genetically modify tumor cells by “severing the leash” that binds the gp96 to the endoplasmic reticulum of the cell and replacing it with a sequence that pumps gp96 out of the cellEnables living cancer cells to “pump-out” their own surface antigens along with the gp96 chaperoneThis process mimics necrotic cell deathActivates a powerful pan-antigen cytotoxic T-cell immune response  Heat Biologics ImPACT® technology reprograms cancer cells to continuously secrete their own antigens bound to heat shock protein gp96  Heat Biologics ImPACT technology removes the leash that binds gp96 to the cell, replacing with a sequence that allows cells to continually secrete gp96 along with their “chaperoned” antigens  Heat’s gp96 ImPACT Therapy  Severing the Leash 

   19  Heat Biologics  ImPACT Mechanism of ActionJeff Hutchins PhDChief Scientific OfficerFebruary 28, 2018 

 20  ImPACT/ComPACT Manufacturing 

 21  ImPACT: Immune Pan-antigen Cytotoxic Therapy 

 Successful Immuno-oncology: A 3 Legged Stool  22 

 ImPact Generates an Adaptive Immune Response  Secretion of gp96-Ig carrying tumor specific proteins represented on the patients tumor.Activation of APCs (TLR2/4) and cross- presentation of antigens (CD91).Specific T-cell receptor engagement.Clonal Expansion of Tumor Antigen Specific T cells.    23 

 Clinical Proof of Mechanism in NCSLC  24    Increased levels of CD8+ T cells deep into the tumorTumors with no previous immune activation made highly activeAssociation with radiographic clinical response        Histopathological evidence that HS-110 is turning COLD tumors HOT 

 25  ImPACT + Opdivo Combination Therapy  The potential to improve clinical responses and survival, without additional toxicity  

 Strong support for our clinical approaches  Pre-clinical Data of T-cell Expansion  26  Source: Fromm et al. Society for Immunotherapy of Cancer Annual Meeting, 2016  CD8+ T-cell Expansion  Higher T-cell responses observed in mice treated with ImPACT aloneImPACT boosted CD8+ T-cells to even higher levels when combined with co-stimulator agonist antibodies: OX40, TNFRSF25, PD-1Findings suggest synergies when combining ImPACT with Pelican’s TNFRSF25 antibody       

   27  Heat Biologics  DURGA Interim Data ReviewGeorge Peoples MD FACSChief Medical OfficerFebruary 28, 2018 

 HS-110-102 DURGA Trial  Objective  Evaluate objective response rate of HS-110 with a PD-1 checkpoint inhibitor (nivolumab)    Design  Single arm multicenter trial of up to 120 patientsCohort analysis based on histology, prior checkpoint inhibitor therapy, TIL levels and PD-L1 expression    Endpoints  Objective Response Rate (RECIST 1.1)Duration of ResponseProgression-free Survival  Overall SurvivalImmune ResponseSafety & Tolerability  Population  Previously treated, advanced NSCLCCurrent Analysis:AdenocarcinomaCheckpoint inhibitor naïveNew Populations for enrollment:Squamous cell carcinomaCheckpoint inhibitor relapsed     A Phase 1b/2 Study of Viagenpumatucel-L (HS-110) in Combination with Multiple Treatment Regimens in Patients with Non-Small Cell Lung Cancer (The “DURGA” Trial) 

 DURGA Schema  X = CT Scan    = Biopsy (or recent archival tissue at baseline)  KEY:  Nivolumab:  HS-110:  Biopsies:  CT Scans:  Timepoint: 

 Pre-Specified Patient Populations Analyzed  ITT (n=35)The Intent-to-Treat Population includes all patients enrolled into the study  PP (n=26)The Per Protocol Population includes patients who have received at least 6 doses of HS-110 and a pre/post treatment tumor assessment      3 patients died before completing 6 weeks of treatment (2 PD & 1 MI)4 patients had no follow-up scans due to clinical progression2 patients had no follow-up scans due to AEs 

 ImPACT (HS-110) Safety Profile to Date 

 Primary Efficacy Analysis  Population  Objective Response Rate (RECIST 1.1)  Disease Control Rate (RECIST 1.1)  ITT (n=35)  17%  40%  PP (n=26)  23%  50%  ORR: Objective Response Rate is defined as the % of patients who have reached Partial Response (PR) per RECIST 1.1 which requires a 30% reduction in the sum of the longest diameters of all target lesions from baseline.DCR: Disease Control Rate is defined as the % of patients who have reached Partial Response (PR) or Stable Disease (SD) per RECIST 1.1 which requires that the sum of the longest diameters of all target lesions does not increase more than 20% from baseline. 

 Best Target Lesion Response  Change from Baseline (%)  All evaluable ITT patients with a baseline and on-treatment scan (n=27) ORR (26%) and disease control (67%) 

 Durable Target Lesion Response  Change from Baseline (%)  All enrolled patients (ITT) with a baseline and on-treatment scan  Days From First Dose  All evaluable ITT patients with a baseline and on-treatment scan (n=27) Overall responses are durable and long lasting (> 6 months) 

 ITT Overall Survival: Encouraging and Still Maturing  ITT survival curve has not yet reached medianm(OS) of nivolumab alone = 12.2 months  mOS nivolumab12.2 months*    *N Engl J Med 2015; 373: 1627-1639 

 PP Overall Survival: Encouraging and Still Maturing  PP survival curve has not yet reached medianm(OS) of nivolumab alone = 12.2 months  mOS nivolumab12.2 months*    *N Engl J Med 2015; 373: 1627-1639 

 Target Lesion Response Based on Initial TIL Status  Change from Baseline (%)  Evaluable ITT Population  Change from Baseline (%)        High TIL  Low TIL  HS-110 shows effect in low TIL “cold tumor” patients who typically do not respond well to PD-1 inhibitors4 of 9 achieved a partial clinical response 

 Durable Target Lesion Responses Based on Initial TIL Status  Low TIL  High TIL  Change from Baseline (%)  Tumor Type at Baseline  Evaluable ITT Population  Days from First Dose  Durable responses (> 6 months) observed in difficult-to-treat low TIL “cold” patients 

 Target Lesion Response Based on Initial PD-L1 Status  Change from Baseline (%)  Evaluable ITT Population  Change from Baseline (%)  >1% PD-L1 Tumor Type at Baseline  <1% PD-L1 Tumor Type at Baseline  High PD-L1  Low PD-L1  HS-110 shows effect in low PD-L1 patients, who typically do not respond to checkpoint inhibitors 

 Durable Target Lesion Responses Based on Initial PD-L1 Status  Change from Baseline (%)  Evaluable ITT Population  Days from First Dose  Change from Baseline (%)  Days from First Dose  >1% PD-L1 Tumor Type at Baseline  <1% PD-L1 Tumor Type at Baseline  Durable responses observed in difficult-to-treat low PD-L1 patients  High PD-L1  Low PD-L1 

 ELISPOT Activity and Survival  High = ELISPOT activity above the median of patients tested Low = ELISPOT activity below the median of patients tested  A trend of survival benefit is observed higher ELISPOT activity of immune response  203  337 

 Summary of Interim Data  Tumor shrinkage and disease control demonstrated in a majority of evaluable patientsOverall responses are durable and long lastingWhile survival data is still maturing, the median overall survival has not yet been reachedHS-110 shows durable responses in difficult-to-treat low TIL “cold tumor” patientsHS110 shows durable responses in low PD-L1 patients, who typically do not respond to checkpoint inhibitorsA trend of survival benefit is observed with higher ELISPOT activity reflective of tumor antigen-specific immune response  This data is consistent with HS-110 mechanism of action as well as data previously reported in our phase 1 trial