On November 9, 2018 Asterias Biotherapeutics, Inc. (NYSE American: AST), a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with demyelination and cellular immunotherapies to treat cancer, reported financial and operational results for the third quarter ended September 30, 2018 (Press release, Asterias Biotherapeutics, NOV 9, 2018, View Source [SID1234531180]).

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On November 7, 2018, Asterias entered into a merger agreement under which Asterias will become a wholly-owned subsidiary of BioTime, Inc. (NYSE American and TASE: BTX) and each outstanding share of common stock of Asterias not already owned by BioTime will be converted into 0.71 common shares of BioTime. The transaction is expected to close during the Company’s first quarter ending March 31, 2019, subject to the satisfaction of customary closing conditions.

Third Quarter 2018 Financial Results

Research and development expenses were $3.5 million in the third quarter. General and administrative expenses were $1.9 million in the third quarter. Total operating expenses were $5.4 million in the third quarter of 2018, compared to $8.7 million in the third quarter of 2017.

Net loss was $4.5 million, or $0.08 per share for the third quarter of 2018 compared to a net loss of $6.8 million, or $0.14 per share for the third quarter of 2017. For the quarter ended September 30, 2018, net cash used in operating activities was $2.9 million compared to $4.5 million for the quarter ended September 30, 2017.

On September 28, 2018, the Company entered into two new agreements with an affiliate of Novo Nordisk, a multinational pharmaceutical company based in Denmark, which included a $2.0 million upfront payment that was received in early October 2018. Following the receipt of such funds from the Novo transaction, on October 1, 2018 the Company had cash and cash equivalents of $8.5 million and $6.2 in marketable equity securities. The Novo transaction will also result in approximately $1.0 million of annual reduction in fixed overhead allowing Asterias to advance its development programs more cost-effectively.

Conference Call

As a result of the merger agreement with BioTime, the Company’s previously announced conference to provide an overview of the third quarter results as well as the recent corporate progress, scheduled for Monday, November 12, 2018 at 5:00pm ET have been cancelled.

On November 9, 2018 Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company that develops antibody-based drug candidates for tumor-directed immunotherapy and Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company that develops new treatments in immunology and hematology, reported that new preclinical data for ALG.APV-527 will be presented at the 33rd Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Scientific Conference, held in Washington, DC, USA, November 9-11, 2018 (Press release, Alligator Bioscience, NOV 9, 2018, View Source [SID1234531196]).

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ALG.APV-527 is a drug candidate for immunotherapeutic treatment of 5T4 positive solid cancer tumors. It is designed to activate the immune system via the co-stimulating receptor 4-1BB (CD137) on activated cytotoxic T cells and NK (Natural Killer) cells. ALG. APV-527 is designed to induce a powerful and tumor-directed immunoreactivation in the presence of 5T4 positive tumor cells. 5T4 is a tumor antigen found in a variety of malignant tumor types.

Preclinical data show that ALG.APV-527 is located in 5T4 positive tumors and selectively stimulates and enhances tumor-responsive immune responses of T cells and NKs, providing powerful anti-tumor effects. In brief, the preclinical data shows that ALG.APV-527 in the presence of 5T4 positive cells:

Increases the ability of CD8 positive T cells to secrete pro-inflammatory cytokines such as IFN gamma
Strengthens NK cell’s cell killability
In addition, the new data confirm that the 5T4 antigen is found in a variety of tumor types. 5T4 positive tumor cells were detected in non-small cell lung cancer (NSCLC) tumor, head and neck cancer, mesothelioma, pancreatic, bladder, kidney and ovarian cancer, but not in normal tissue samples such as liver and heart.

"Recent preclinical results further enhance ALG.APV-527’s potential for targeting 5T4 positive tumors and selectively activating the immune system via tumor-specific activation of T cells and NK cells. Overall, this gives potential for better anti-tumor effect with less side effects. We are now compiling a preclinical data packet with the goal of submitting a clinical trial (CTA) clinical trial in the second half of 2019, "said Christina Furebring, Senior Vice President Research at Alligator.

"Our new bispecific drug candidate ALG.APV-527 continues to show promising results in preclinical in vitro and in vivo studies. It exhibits properties such as goal-directed T-cell activation, optimized stability, an antibody-like half-life of 9 days, and good production characteristics. Aptevo and Alligator believe that this gives ALG.APV-527 a potential to become a unique anti-cancer drug for the treatment of several 5T4 expressive solid tumors, where there is today a major medical need. We are looking forward to submitting a CTA next year and then commencing clinical studies, "said Jane Gross, Chief Scientific Officer at Aptevo.

Alligator / Aptevos poster presentation titled "Potent Tumor-Directed T Cell Activation and Tumor Inhibition Induced by a 4-1BB x 5T4 ADAPTIR Bispecific Antibody " will be presented today November 9th from 18.45 to 14.45 (12.45-14.45 local) time) and from kl.30.30 to 2.30 (18.30-20.30 local time).

For more information, see View Source .

For further information please contact:
Cecilia Hofvander, Director Investor Relations & Communications
Telephone: 046-286 44 95
Email: [email protected]

This information is the information that Alligator Bioscience AB (publ) is obliged to disclose under the EU Market Abuse Regulation and the Securities Market Act. The information was provided, through the contact of the above contact person, for publication on November 9, 2018, at 06:00.

About ALG.APV-527
ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor directed treatment of solid cancer tumors. ALG.APV-527 was constructed by combining Alligator’s antibody library ALLIGATOR-GOLD and Aptevo’s bispecific technology ADAPTIR . The antibody ALG.APV-527 consists of two parts, one activating tumor-specific T cells via the co-stimulating receptor 4-1BB (CD137) and the other binding to the protein 5T4 on the surface of tumor cells. This controls the immune activating effect of ALG.APV-527 to the tumor and not to normal tissue.

On November 9, 2018 Nektar Therapeutics (Nasdaq: NKTR) reported a presentation of new clinical and preclinical data for its I-O pipeline at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Nektar Therapeutics, NOV 9, 2018, View Source [SID1234531214]).

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New clinical study results from the PIVOT-02 Phase 1/2 Study were shared in an oral presentation titled, "Immune monitoring after NKTR-214 plus nivolumab (PIVOT-02) in previously untreated patients with metastatic Stage IV melanoma" (Abstract #O4) by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center during the Cytokines Reinvented Session on Friday, November 9th.

Additional preclinical data presented at the annual meeting showed that NKTR-214 may drive, sustain and expand anti-tumor response when combined with therapies with complementary mechanisms of action including NKTR-262, poly (ADP-ribose) polymerase (PARP) inhibitors, radiation therapy (RT) and other agents. When combined with these treatments, NKTR-214 showed the potential to lead to tumor clearance and tumor specific immunologic memory.

"The data presented at this year’s SITC (Free SITC Whitepaper) Annual Meeting showcase our pipeline of novel investigational I-O agents that target key components of the immune cycle in order to restore immune surveillance and harness the body’s immune system to fight cancer," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Scientific Officer at Nektar Therapeutics. "Clinical data presented for NKTR-214 show that NKTR-214 plus nivolumab give deep and durable responses in first-line IO-naive Stage IV melanoma patients, including a high rate of complete responses. For our TLR agonist candidate, NKTR-262, we presented data demonstrating alteration of the tumor micro-environment, including activating the innate and adaptive arms of the immune system along with encouraging anti-tumor activity."

Highlights from the oral presentation on Stage IV 1L Melanoma patients include:

Clinical Efficacy (Response measured per RECIST 1.1 by central independent radiology review for efficacy-evaluable patients treated at the recommended Phase 2 dose and with >1 on treatment scan). Response and median time on study calculated from data cut as of October 1, 2018:

Confirmed best overall response rate (ORR) was 53% (20/38) in efficacy-evaluable patients, with a 24% (9/38) complete response (CR) rate. Median time of follow-up was 7.2 months and median time to response was 2 months. 85% (17/20) patients with responses have ongoing responses. DCR, also known as disease control rate (CR+ PR + SD) was 76%.
Amongst the 33 patients with known pre-treatment PD-L1 status, ORR in PD-L1 negative patients was 6/14 (43%) and in PD-L1 positive patients was 13/19 (68%). One patient with unknown PD-L1 baseline status experienced a CR.
Clinical Safety (1L Melanoma safety database as of October 1, 2018):

A total of 41 patients have been treated at the RP2D. The most common (>30%) treatment-related adverse events (TRAEs) were grade 1-2 flu-like symptoms (78%), rash (70.7%), fatigue (63.4%), pruritus (46.3%), nausea (43.9%), arthralgia (36.6%) and myalgia (31.7%). A total of 8/41 (19.5%) of patients experienced a Grade 3 (G3) or higher TRAE with 2/41 (4.9%) patients discontinuing treatment due to a TRAE. 2/41 (4.9%) of patients experienced a G3 or higher immune-mediated AE.
A decreased frequency of Grade 1-2 cytokine related AEs was observed with continuous dosing.
Biomarkers and Mechanism of Action:

Clear activation of the IL-2 pathway demonstrated by an increase in absolute lymphocyte count with activated and proliferating CD4, CD8 and NK cells in blood.
Combination demonstrated T cell infiltration and activation in the tumor microenvironment.
TCR repertoire analysis demonstrates the presence of newly trafficked clonal infiltrates after treatment with NKTR-214 plus nivolumab.
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. NKTR-214 is an investigational immuno-stimulatory therapy designed to expand and activate specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of cell-surface PD-1 on these immune cells. A Phase 3 trial evaluating NKTR-214 in combination with nivolumab versus nivolumab in first-line advanced melanoma patients is currently recruiting patients (NCT03635983).

A copy of Dr. Diab’s presentation of PIVOT-02 data is available on Nektar’s corporate website at View Source

Details of the preclinical poster presentations at SITC (Free SITC Whitepaper) are as follows and each will be available for download at the time of presentation at View Source

Poster/Abstract #P364: "Systemic anti-tumor immunity and immune memory formation by a novel TLR7/8 targeting agent NKTR-262 combined with CD122-biased immunostimulatory cytokine NKTR-214", Kivimae, S., et al.

NKTR-262 and NKTR-214 in combination showed efficacy in all tested preclinical tumor models, correlated with sustained systemic expansion of tumor antigen specific CD8+ T cells.
Combining NKTR-262 with NKTR-214 coordinates tumor antigen presentation and costimulatory signaling with tumor antigen recognizing CD8+ T cell expansion to produce a sustained systemic anti-tumor immune response.
Poster/Abstract #P378: "NKTR-214 (CD122-biased agonist) and NKTR-262 (TLR7/8 agonist) combination treatment pairs local innate immune activation with systemic CD8+ T cell expansion to enhance anti-tumor immunity", Rolig, A., et al.

NKTR-214 and NKTR-262 resulted in systemic CD8+ T cell expansion, enhanced intratumoral CD8+ T cell effector function, and favorable myeloid polarization.
This robust anti-tumor immunity resulted in improved tumor regression and tumor-free survival in preclinical models.
Poster/Abstract #P368: "Combination of a Dipeptidyl Peptidase Inhibitor BXCL701 and Biased CD122 Agonist NKTR-214 with Anti-PD1 Provides Functional Immunological Memory through Inflammatory Cell Death", MacDougall, J., et al.

In a triple combination with NKTR-214 and an anti-PD-1 antibody, BXCL701 generated complete and durable responses in models with high densities of tumor associated. macrophages, validating the importance of engaging multiple cell types of the immune system required for complete anti-tumor response.
Poster/Abstract #P348: "Survival and immune modulation in homologous recombination deficient murine ovarian tumors using the PARP inhibitor, rucaparib and immune agonist, NKTR-214", Charych, D., et al.

NKTR-214 paired with rucaparib provided significantly increased survival and durable complete response than either treatment alone in murine models of ovarian cancer.
Preclinical results suggest the activity of this combination is through antigen priming of infiltrating memory T cells, increased NK cell recruitment and enhanced cytotoxicity of tumor infiltrates.
Poster/Abstract #P418: "Pre-clinical investigation of NKTR-255, a polymer-conjugated IL-15 with a potent NK cell dependent anti-tumor efficacy", Miyazaki, T., et al.

NKTR-255 demonstrated powerful immune stimulation of NK cells with dose-dependent effect in the proliferation and activation of NK cells and enhanced anti-metastatic activity in mouse lung metastasis models.
Results suggest NKTR-255 has high promise as a novel anti-tumor agent that boosts NK cell expansion and survival.
Poster/Abstract #P419: "NKTR-214 in combination with radiation produces a potent in situ vaccine in the syngeneic B78 melanoma model", Sondel, P., et al.

In a murine melanoma model study, the combination of NKTR-214 and radiation therapy (RT) resulted in significant tumor regression, higher rates of complete response, and stronger immunologic memory compared with radiation RT, RT plus IL-2, or NKTR-214 alone.
Poster/Abstract #P422: "A polymer-associated human IL-15 (NKTR-255) has optimized biological activity and unique mechanisms of action on CD8 T Cells and NK Cells", Robinson T., et al.

Preclinical findings highlighted the ability of NKTR-255 to impact different mechanisms of action on CD8 T cells and NK cells leading to novel therapeutic effects.
Poster/Abstract #P424: "NKTR-214, an engineered IL-2, selectively depletes intratumoral Tregs and expands immunotherapy-induced effector T cell responses", Sharma, M., et al.

NKTR-214 showed synergy with both checkpoint blockade and peptide-vaccination resulting in improved overall survival and cure of mice in models of colon carcinoma and melanoma.
The synergistic mechanism led to proliferation and tumor infiltration of effector CD8+ T cells while promoting selective intratumoral depletion of Tregs to establish effective anti-tumor immunity.
Poster/Abstract #P557: "Overcoming genetically-based resistance mechanisms to PD-1 blockade", Torrejón, D., et al.
[NOTE: These data were also presented in an oral presentation titled "Overcoming genetically-based resistance mechanisms to PD-1 blockade" by Davis Torrejón, M.D., UCLA Hematology-Oncology, during the Rapid Oral Abstract Presentations Session on Friday, November 9th.]

Genetic models of resistance to anti-PD-1 therapy were assessed using JAK1, JAK2, and B2M knockout (KO) models.
NKTR-214 overcame resistance to anti-PD-1 in the B2M-KO tumor model and significantly increased survival.
Analyst Call with Melanoma Specialists
Nektar will webcast an analyst and investor conference call with melanoma specialists and company management on Saturday, November 10, 2018 at 9:00 a.m. EST in Washington, D.C. during the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The event follows today’s oral presentation of new efficacy, safety and immune monitoring data from the first-line Stage IV metastatic melanoma patient cohort in the PIVOT-02 study of NKTR-214 in combination with nivolumab.

Date and Time: Saturday, November 10, 2018 at 9:00 a.m. EST
Dial- in: 877-881-2183 (toll-free) or 970-315-0453 (enter access code 7865989)

Clinical investigators on the conference call will include Dr. Harriet Kluger, Professor of Medicine, Medical Oncology at the Yale Cancer Center and Dr. Adi Diab, Assistant Professor, Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center. Investors and analysts can also view slides and listen to the live audio webcast of the presentation at View Source The event will also be available for replay for two weeks on the company’s website, www.nektar.com.

About NKTR-214
NKTR-214 is a CD122-biased agonist designed to stimulate the patient’s own immune system to fight cancer. NKTR-214 is designed to grow specific cancer-killing T cells and natural killer (NK) cell populations in the body which fight cancer, which are known as endogenous tumor-infiltrating lymphocytes (TILs). NKTR-214 stimulates these cancer-killing immune cells in the body by targeting CD122 specific receptors found on the surface of these immune cells, known as CD8+ effector T cells and Natural Killer (NK) cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

About NKTR-262
Cancer treatments that couple pharmacological activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a novel small molecule agonist designed to activate toll-like receptors (TLRs). Intratumoral delivery of NKTR-262 promotes TLR activation to induce the development of antigen-specific immunity by initiating the process by which the immune system generates antigen-specific cytotoxic T cells to the patient’s specific tumor.4 NKTR-214 targets CD122 specific receptors found on the surface of these cancer-killing immune cells, known as CD8+ effector T cells. By first generating antigen-specific cytotoxic T cells with NKTR-262 and then growing these CD8+ effector T cells with NKTR-214, the patient’s entire immunity cycle can potentially be engaged to fight cancer. In preclinical studies, a single intratumoral dose of NKTR-262, administered in combination with NKTR-214, resulted in complete abscopal tumor regressions in multiple mouse syngeneic tumor models.5

About NKTR-255
NKTR-255 is a memory T cell stimulating cytokine designed to engage the IL-15 pathway to induce long-term T cell activation and improve the quality of T cell memory response to treat cancer. Through optimal engagement of the IL-15Rα/IL-2Rγ receptor complex, NKTR-255 stimulates proliferation and survival of CD8+ T cells, natural killer (NK) cells and enhances formation of long-term immunological memory which may lead to sustained anti-tumor immune response. Native rhIL-15 is rapidly cleared from the body and must be administered frequently and in high doses limiting its utility due to toxicity. NKTR-255 is designed with IL-15 receptor alpha specificity to optimize biological activity and is uniquely engineered to provide optimal exposure and an improved safety profile.

On November 9, 2018 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported data from the ongoing Phase 2 clinical trial of mocetinostat in combination with durvalumab (IMFINZI) in non-small cell lung cancer (NSCLC) patients at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington, D.C (Press release, Mirati, NOV 9, 2018, View Source [SID1234531095]). The data will be presented today in a poster and also in an oral presentation on Sunday, November 11th.

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Highlights from the Oral Presentation

The clinical trial is a Phase 2 study evaluating the efficacy and safety of mocetinostat in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, in patients with NSCLC who have experienced documented disease progression following prior treatment with an immune checkpoint inhibitor. As of the data cut-off date of October 2, 2018:

29 patients were evaluable for response with at least one radiographic scan. Patients had a median of two lines of previous therapy.
12/29 evaluable patients demonstrated tumor reductions.
6/29 evaluable patients demonstrated tumor reductions of greater than 30%.
5/29 evaluable patients achieved a confirmed Partial Response (PR).
4/29 evaluable patients, including 2 responding patients, remained on treatment at the time of data cut-off.
A preliminary Kaplan-Meier estimate of median duration of response was greater than 5 months.
The combination has been well-tolerated and most adverse events (AEs) were grade 1 or 2.
"The combination of mocetinostat with durvalumab demonstrated clinical benefit in this difficult to treat population of checkpoint inhibitor refractory NSCLC patients," said Charles Baum, M.D., Ph.D., President and Chief Executive Officer at Mirati Therapeutics. "While these results are promising, we have made the strategic portfolio decision to prioritize sitravatinib for further development in the treatment of checkpoint inhibitor refractory patients and plan to explore collaborative opportunities to further develop mocetinostat."

The Company recently announced plans to initiate a Phase 3 clinical trial comparing sitravatinib in combination with checkpoint inhibitor therapy to docetaxel in second line checkpoint inhibitor refractory NSCLC patients in the first half of 2019. In addition, the Company also announced plans to initiate a Phase 1/2 clinical trial of MRTX849, an oral inhibitor of KRAS G12C, in patients with NSCLC, colorectal cancer, and other solid tumors that harbor the G12C mutation. Trial initiation is planned for early 2019 after the investigational new drug (IND) allowance letter is received from the U.S. Food and Drug Administration (FDA) for the application that was filed in October 2018.

About Mocetinostat

Mocetinostat is an oral, Class I and IV selective histone deacetylase (HDAC) inhibitor. Inhibition of histone acetylation is predicted to enhance the recognition of tumor cells by anti-tumor T cells and reverse immunosuppressive factors in the tumor microenvironment. Mocetinostat is being evaluated in a Phase 2 clinical trial in combination with durvalumab (IMFINZI) in non-small cell lung cancer (NSCLC) patients who have experienced disease progression following prior treatment with a checkpoint inhibitor.

About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion clinical trial emphasizing enrollment of patients whose tumors harbor specific mutations in the CBL protein. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma. Sitravatinib potently inhibits these RTKs and is being investigated as a treatment option for cancer patients with CBL mutations.

About MRTX849

MRTX849 is an orally-available small molecule that potently and selectively inhibits a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients and 5% of colorectal cancer patients. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MTRX849 has demonstrated broad-spectrum tumor regression in a large cohort of KRAS G12C positive, pre-clinical in-vivo human tumor models. MRTX849 demonstrated complete regression of tumors in a subset of models at well-tolerated dose levels. Early proof-of-concept clinical data is anticipated in 2019.

On November 9, 2018 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company developing targeted and immuno-oncology therapeutics, reported a business update and financial results for the third quarter ended September 30, 2018 (Press release, Leap Therapeutics, NOV 9, 2018, View Source [SID1234531197]).

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"Our team has executed extremely well over the past quarter, rapidly enrolling multiple clinical trials and presenting impressive clinical and preclinical data for both of our programs. We are excited about the potential for our DKN-01 antibody in patients with esophagogastric cancer, both in combination with KEYTRUDA (pembrolizumab) and with paclitaxel. We believe that the emerging response and disease control rates, and now the progression-free survival and overall survival data, reflect outcomes that are clinically meaningful to patients with very difficult to treat cancer and are greater than what has previously been demonstrated with approved single agents," commented Christopher K. Mirabelli, Ph.D, President and Chief Executive Officer of Leap Therapeutics. "In addition, we look forward to presenting data from the studies of our TRX518 antibody in combination with KEYTRUDA, OPDIVO (nivolumab) or gemcitabine at the European Society for Molecular Oncology 2018 Immuno-Oncology Congress in December."

Recent Developments

Since the end of the second quarter, the Company has continued to make strong progress with the development of their product candidates.

DKN-01/KEYTRUDA: At the European Society for Molecular Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress, Leap presented clinical data from a study evaluating DKN-01 in combination with KEYTRUDA (pembrolizumab) in patients with advanced esophagogastric cancer. As of the cut-off date for the poster, DKN-01 and pembrolizumab had a 23.5% overall response rate and 58.8% disease control rate in evaluable gastric or gastroesophageal junction cancer patients who have been heavily pre-treated and not received any prior anti-PD-1/PD-L1 therapy. All four of the responding patients had tumors that were microsatellite stable, which is a subgroup of patients who have historically experienced a less than ten percent response rate to KEYTRUDA monotherapy.

DKN-01/PACLITAXEL: At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting, Leap presented an update on a clinical study evaluating DKN-01 in combination with paclitaxel in patients with advanced esophagogastric cancer. The combination of DKN-01 and paclitaxel generated a 46.7% overall response rate, 19.6 weeks median progression free survival, and 61.1 weeks median overall survival in fifteen evaluable patients as a second line therapy. In the benchmark RAINBOW study, paclitaxel monotherapy in second line gastroesophageal junction or gastric cancer patients generated a 16.1% overall response rate, 2.9 months median progression free survival, and 7.4 months median overall survival. Additionally, in our study in the subgroup of twelve evaluable patients with heavily pre-treated esophageal squamous cell carcinoma, the combination of DKN-01 and paclitaxel produced a 33.3% overall response rate, 13.7 weeks median progression free survival, and 31.0 weeks median overall survival.

DKN-01 in HCC: The first patient has been enrolled in Leap’s investigator-initiated study of DKN-01 as a monotherapy and in combination with NEXAVAR (sorafenib) in hepatocellular carcinoma patients with Wnt pathway activation.

TRX518/BAVENCIO: In July, Leap announced a collaboration agreement with Pfizer and Merck KGaA, Darmstadt, Germany to evaluate TRX518 in combination with BAVENCIO (avelumab) and cyclophosphamide chemotherapy. Under the terms of the collaboration, Leap will be conducting a Phase I/II clinical trial in advanced solid tumors including expansion populations in patients with relapsed/refractory ovarian, breast, and prostate cancers.

· TRX518/KEYTRUDA or OPDIVO or GEMCITABINE: During the third quarter, Leap presented initial data from a clinical trial evaluating TRX518 in combination with gemcitabine chemotherapy or in combination with KEYTRUDA (pembrolizumab) or OPDIVO (nivolumab). Three patients treated with TRX518 in combination with anti-PD1 antibodies have experienced clinical benefit. An esophageal squamous cell carcinoma patient treated with TRX518 and KEYTRUDA demonstrated a partial response with a 77% reduction in tumor volume, and an ocular melanoma patient experienced stable disease with a 23% reduction in tumor volume. An urothelial carcinoma patient who had progressed while on KEYTRUDA has had a partial response with TRX518 and OPDIVO with a 39% reduction in tumor volume. We have also fully enrolled the TRX518 and gemcitabine expansion cohort. We plan to present additional data from this trial at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress in December 2018.

Selected Third Quarter 2018 Financial Results

Net loss was $6.6 million for the third quarter of 2018, compared to $6.8 million for the same period in 2017.

Research and development expenses were $6.5 million for the third quarter 2018, compared to $6.8 million for the same period in 2017. The decrease of $0.3 million was primarily due to a decrease of $1.3 million in manufacturing costs related to clinical trial material. This decrease was partially offset by an increase of $0.7 million in clinical trial costs, an increase of $0.2 million in payroll and other related costs and an increase of $0.1 million in stock based compensation expense.

General and administrative expenses were $2.1 million for the third quarter 2018, compared to $1.8 million for the same period in 2017. The increase of $0.3 million in general and administrative expenses was primarily due to a $0.2 million increase in stock based compensation expense and an increase of $0.1 million in legal, audit and consulting fees associated with corporate and business development activities.

Cash, cash equivalents and marketable securities totaled $23.2 million at September 30, 2018. Research and development incentive receivables totaled $2.1 million. In October 2018, we received $0.8 million of research and development tax incentive payments from the Commonwealth of Australia. We anticipate that our current cash resources will extend until late in the third quarter of 2019.