On November 12, 2021 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported financial results for the third quarter ended September 30, 2021 (Press release, Leap Therapeutics, NOV 12, 2021, View Source [SID1234595339]).

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Leap Third Quarter Highlights:

Completed a $103.6 million public offering of common stock and pre-funded warrants to purchase common stock, resulting in net proceeds of $96.8 million
Presented positive initial data from the DisTinGuish Study of DKN-01 plus tislelizumab and chemotherapy in gastric cancer patients at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021
"We presented positive new data at ESMO (Free ESMO Whitepaper) of DKN-01 in combination with BeiGene’s tislelizumab and chemotherapy demonstrating compelling overall response rates in patients with first-line gastric or gastroesophageal junction (G/GEJ) cancer, particularly those patients whose tumors expressed high levels of DKK1 or low PD-L1," said Douglas E. Onsi, President and Chief Executive Officer of Leap. "We look forward to presenting additional data from the DisTinGuish study early next year and aggressively advancing DKN-01 into the next stages of development in G/GEJ and other cancers."

Business Update

Leap Completed a $103.6 Million Public Offering of Common Stock and Pre-Funded Warrants to Purchase Common Stock – In September 2021, Leap announced the commencement and closing of an underwritten public offering of 27,568,072 shares of its common stock, including the sale of an additional 4,740,000 shares of its common stock pursuant to the full exercise of the underwriters’ option to purchase additional shares, and of pre-funded warrants to purchase 8,771,928 shares of its common stock. Aggregate gross proceeds to Leap from the offering were $103.6 million, including $7.25 million invested by its collaborator and existing investor BeiGene, Ltd., resulting in net proceeds after underwriting discounts and commissions and offering expenses of $96.8 million.
DKN-01 Clinical Milestones

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways, which play an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells.

Initial Data from the DisTinGuish Clinical Trial of DKN-01 Plus Tislelizumab and Chemotherapy Presented at ESMO (Free ESMO Whitepaper) Congress 2021. The Company presented initial positive data from the first-line cohort of the Phase 2a study in patients with G/GEJ cancer. Of the 25 first-line HER2- G/GEJ patients who received a full cycle of DKN-01 therapy, overall response rate (ORR) was 68.2%, with 90% ORR in DKK1-high patients and 56% in DKK1-low patients. Among those patients with PD-L1-low expression, ORR was 79% (with 100% ORR in DKK1-high patients and 57% ORR in DKK1-low patients), and in patients with PD-L1-high expression, ORR was 67% (with 75% ORR in DKK1-high patients and 50% in DKK1-low patients), suggesting response to DKN-01 was independent of PD-L1 expression.
Selected Third Quarter 2021 Financial Results

Net Loss was $11.1 million for the third quarter 2021, compared to $7.1 million for the same period in 2020.

License revenues were $0.4 million for each of the third quarter 2021 and the same period in 2020, and relate to the Agreement with BeiGene for the development and commercialization of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.

Research and development expenses were $10.1 million for the third quarter 2021, compared to $5.4 million for the same period in 2020. The increase of $4.7 million in research and development expenses was due to an increase of $3.3 million in manufacturing costs related to clinical trial material due to timing of manufacturing campaigns, an increase of $0.7 million in clinical trial costs due to timing of patient enrollment, an increase of $0.6 million in payroll and other related expenses due to an increase in headcount of our research and development full time employees, and an increase of $0.1 million in stock based compensation expense due to new stock options granted to research and development full time employees in 2021.

General and administrative expenses were $2.4 million for the third quarter 2021, compared to $2.5 million for the second quarter 2020. The decrease of $0.1 million in general and administrative expenses was due to a $0.4 million decrease in professional fees partially offset by an increase of a $0.2 million in stock based compensation expense due to new stock options granted to general and administrative full time employees in 2021 and an increase of $0.1 million in payroll and other related expenses.

Cash and cash equivalents totaled $124.8 million at September 30, 2021. Research and development incentive receivables totaled $1.6 million at September 30, 2021.

On November 12, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported additional clinical data for its tumor infiltrating lymphocyte (TIL) therapy LN-145 in patients with metastatic non-small cell lung cancer (mNSCLC) who enrolled in Cohort 3B of the ongoing basket study IOV-COM-202 (Press release, Iovance Biotherapeutics, NOV 12, 2021, View Source [SID1234595338]). The results are available in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, November 12-14, 2021, Washington, D.C. and virtual.

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The results demonstrate the feasibility of TIL cell therapy in heavily pre-treated patients with NSCLC, and warrant continued investigation of LN-145 as a single-agent and in combination in patients with mNSCLC in ongoing Iovance clinical studies IOV-LUN-202 and IOV-COM-202.

Adam J. Schoenfeld, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center and an investigator in the IOV-COM-202 and IOV-LUN-202 studies, stated, "The clinical data for LN-145 in heavily-treated patients with metastatic non-small cell lung cancer is exciting. It represents the first experience for TIL monotherapy to show clinical benefit in metastatic non-small cell lung cancer and demonstrates the feasibility and safety shown in a multi-center study with a centralized manufacturing process. I am particularly impressed to see responses following multiple prior therapies, including tumors resistant to anti–PD-(L)1 blockade. We observed responses to LN-145 across a range of PD-L1 expression levels, clinical characteristics, and molecular features. I look forward to the ongoing IOV-LUN-202 clinical study in second-line non-small cell lung cancer, where there’s potential to see an increase in overall responses and durability among patients who are earlier in their disease and improve a treatment landscape dominated by chemotherapy."

Following one-time treatment with LN-145 monotherapy, the overall response rate (ORR) is 21.4% in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24), including one complete response and five partial responses (August 24, 2021 data cutoff). Two responders, including the CR, had PD-L1 negative tumors and two responders had tumors with KRAS mutations. One complete response and one partial response are ongoing at 20.7 months and 3.0 months, respectively, at a median study follow up of 9.8 months. The treatment-emergent adverse event profile is consistent with the underlying disease and known adverse event profiles of non-myeloablative lymphodepletion and IL-2.

The heavily pre-treated patients in Cohort 3B had received a median of 2 prior therapies. All patients had progressed on prior immune checkpoint inhibitor (ICI) therapy and all six responders received prior chemotherapy. TIL were most commonly grown and manufactured from tumor samples resected from the lung.

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "We are pleased to present our clinical data for LN-145 in metastatic non-small cell lung cancer to the physician community at SITC (Free SITC Whitepaper). There remains a very significant unmet need to increase response rates and prolong survival in the second-line non-small cell lung cancer treatment setting. The data for LN-145 in this signal-finding cohort demonstrated the potential for TIL in metastatic non-small cell lung cancer across a diverse set of patients and informed our ongoing IOV-LUN-202 clinical study in second-line lung cancer. Iovance is committed to advancing both TIL alone and TIL combinations to address multiple non-small cell lung cancer patient populations."

Iovance is currently enrolling patients in the IOV-LUN-202 clinical study to investigate LN-145 in second-line mNSCLC where patients have progressed on prior ICI and chemotherapy. More than 20 clinical sites are currently active in the U.S. and Canada. For more information please visit Iovance.com/clinical or clinicaltrials.gov (identifier NCT04614103).

Iovance Posters and Presentations at SITC (Free SITC Whitepaper) Annual Meeting (November 12-14, 2021)

Title: Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers
Authors: D O’Malley, et al.
Presentation Type: Oral Presentation
Date and Time: Saturday, November 13, 2021 at 4:30 p.m. ET
Abstract ID: 492

Title: First phase 2 results of autologous tumor-infiltrating lymphocyte (TIL; LN-145) monotherapy in patients with advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer (NSCLC)
Authors: A Schoenfeld, et al.
Presentation Type: Poster (available online)
Abstract ID: 458

Title: Successful generation of tumor-infiltrating lymphocyte (TIL) product from renal cell carcinoma (RCC) tumors for adoptive cell therapy
Authors: B Halbert, et al.
Presentation Type: Poster (available online)
Abstract ID: 176

Title: Expansion of tumor-infiltrating lymphocytes (TIL) using static bag for the clinical manufacturing rapid expansion protocol (REP) process
Authors: K Onimus, et al.
Presentation Type: Poster (available online)
Abstract ID: 101

Conference Call and Webcast on Saturday, November 13, 2021 at 5:30 p.m. ET

Iovance will host a webcast and conference call on Saturday, November 13, at 5:30 p.m. ET to discuss SITC (Free SITC Whitepaper) clinical data updates for Iovance TIL in relapsed, refractory lung cancer as well as Iovance TIL in combination with pembrolizumab in patients with advanced cancers.

Iovance senior leadership will be joined by the following key opinion leaders and principal investigators in Iovance clinical studies:

Omid Hamid, M.D., Chief of Research/ImmunoOncology, The Angeles Clinic and Research Institute; Co-Director, Cutaneous Malignancy Program, Cedars Sinai CANCER
David M. O’Malley, M.D., Professor of Obstetrics and Gynecology at The Ohio State University College of Medicine; Director of the Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)
Adam J. Schoenfeld, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center
The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 3263399. The live webcast can be accessed in the Investors section of the company’s website at www.iovance.com. The archived webcast will be available for one year following the event.

On November 12, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results from an immunologic analysis of Phase 2 study data showing that trilaciclib enhances both CD4 and CD8 T cell function in certain patients with metastatic triple negative breast cancer (mTNBC) when administered prior to chemotherapy (Press release, G1 Therapeutics, NOV 12, 2021, View Source [SID1234595337]). Patients receiving placebo prior to chemotherapy did not demonstrate enhanced T cell function . Results of the immunologic analysis are being presented in a poster session at the 36th Annual Meeting of The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), Nov. 10-14, 2021. The poster is available in the scientific publications section of the G1’s website.

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"The Phase 2 immunologic data analysis suggests that administering trilaciclib prior to chemotherapy may enhance antitumor efficacy by modulating the composition and response of immune cell subsets," said John Yi, PhD, Director of Translational Medicine at G1 Therapeutics.

In the exploratory analysis, researchers sought to investigate the immune mechanisms underlying the improved rate of overall survival shown in the 2020 Phase 2 trial of TNBC patients receiving trilaciclib in combination with gemcitabine/carboplatin (GCb) compared with GCb alone. The researchers evaluated tumor samples and peripheral blood samples from patients at baseline and after trilaciclib/GCb administration or after placebo/GCb administration to identify differential gene expression and changes in immune function between the two groups. Further, they measured qualitative and quantitative differences between patients who did respond or did not respond to trilaciclib plus GCb. Response to treatment was defined as partial or complete response, while nonresponse was defined as stable or progressive disease.

Among the findings in the poster titled, "Immune Profiling to Investigate Improved Survival in Patients with Metastatic Triple-Negative Breast Cancer Receiving Trilaciclib Prior to Chemotherapy":

Patients who received trilaciclib prior to GCb showed increased T cell function as measured by greater production of inflammatory cytokines
Patients who received trilaciclib had fewer immune suppressing cells known as myeloid-derived suppressor cells (MDSCs) than patients who received GCb alone, whether they were responders or non-responders to treatment
Non-responders to trilaciclib/GCb had a reduction in circulating CD4 and CD8 T cells and a decreased production of inflammatory cytokines
"It is critical that we fully understand the underlying immune mechanisms that contributed to the overall survival improvement that was seen in the Phase 2 mTNBC trials, and to identify biomarkers that will clearly distinguish between trilaciclib responders and non-responders," said Dr. Yi. "We are further investigating the impact of trilaciclib on changes to the tumor-infiltrating immune response in our Phase 3 PRESERVE 2 trial in patients with mTNBC and in a planned mechanism-of-action trial in the neoadjuvant TNBC setting."

About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15% to 20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because TNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating TNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with TNBC compared to other forms of breast cancer, and TNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On November 12, 2021 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported updated results from its Phase 1/1b clinical trial of mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed unique mechanism of activating B cells to generate immune responses to tumor antigens and viruses, and inhibiting the production of immunosuppressive adenosine in the tumor microenvironment (Press release, Corvus Pharmaceuticals, NOV 12, 2021, View Source [SID1234595334]). The clinical data, along with pre-clinical data, further strengthen mupadolimab’s mechanism of action and demonstrate its potential anti-tumor activity in cancer patients.

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The data were made available today in an on-demand, electronic poster format for registered participants of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, which is taking place from November 10 to 14, 2021. The poster is also being presented in-person at SITC (Free SITC Whitepaper) by Jason J. Luke, M.D., principal investigator of the trial and Director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center and Associate Professor of Medicine at the University of Pittsburgh School of Medicine.

"We continue to broaden our understanding of mupadolimab’s unique characteristics as an anti-CD73 antibody that exhibits potent blockade of adenosine production as well as powerful adenosine-independent effects on the immune system that result in enhanced B cell and T cell function," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "Recent research has demonstrated that B cells have a vital role in the immune response to tumors from non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers (HNSCC) each frequently containing high numbers of B cells in the tumor and tumor microenvironment. In our Phase 1/1b clinical trial, treatment with mupadolimab in these cancers resulted in tumor regression in patients that failed to respond to, and progressed through prior treatment with anti-PD(L)-1 therapy. This suggests that, in some patients, mupadolimab’s novel mechanism of action may overcome resistance to anti-PD(L)1 therapies."

Dr. Miller added, "In addition, the results presented at SITC (Free SITC Whitepaper) provide important data on the immunologic effects of mupadolimab, as well as pharmacokinetic, pharmacodynamic and safety data for monotherapy and combination therapy. Looking forward, we are now enrolling additional patients with HNSCC and NSCLC in expansion cohorts. These patients will receive the combination of mupadolimab and pembrolizumab and we anticipate reporting results from these expansion cohorts in early 2022. We believe that the data presented at SITC (Free SITC Whitepaper) and data obtained from ongoing expansion cohorts may provide the rationale for a randomized controlled study of mupadolimab, which we expect could begin in 2022."

Mupadolimab Phase 1/1b Clinical Trial Key Results Presented at SITC (Free SITC Whitepaper) 2021
Mupadolimab is being studied in a Phase 1/1b clinical trial in patients with a variety of advanced, refractory cancers, including NSCLC and HNSCC that have failed previous treatment with anti-PD-1 therapy and chemotherapy. The study design included mupadolimab dose escalation from 1 mg/kg to 24 mg/kg intravenous infusion every 3 weeks until disease progression or dose limiting toxicities were reached. Cohorts of patients were treated with mupadolimab monotherapy; combination with ciforadenant, Corvus’ small molecule inhibitor of the A2A receptor; combination with pembrolizumab; or triplet combination with ciforadenant and pembrolizumab.

The data presented at SITC (Free SITC Whitepaper) showed that mupadolimab doses of 12mg/kg are optimal, resulting in complete occupancy of the CD73 target and maximal effects on B cell activation. In the assessment of anti- tumor activity in patients receiving optimal doses of mupadolimab, tumor regression (not meeting the threshold for partial response by RECIST) was seen in five patients who had progressive disease as best response to most recent therapy, which included anti-PD(L)1 therapy (see waterfall plot below). This indicates that tumor regression could occur in patients with tumors refractory to anti-PD(L)1 that are treated with mupadolimab.

A figure accompanying this announcement is available at View Source

"The findings of tumor regression with mupadolimab in patients who had grown through their most recent prior therapy with an anti-PD(L)1 is noteworthy. This supports the possibility that mupadolimab’s mechanism of action could serve to add to effectiveness or overcome limitations of current anti-PD(L)1 therapies. This activity would be expected to be more impactful in patients treated earlier in their disease, with less prior therapies," said Dr. Luke. "We look forward to expanding our experience with mupadolimab in combination with anti-PD(L)-1 in earlier lines of therapy."

Additional mupadolimab oncology program highlights from the SITC (Free SITC Whitepaper) poster presentation include:

Pharmacokinetic (PK) and pharmacodynamic (PD) results showed complete CD73 target occupancy with mupadolimab at doses of 12 mg/kg and higher. Doses up to 18 mg/kg were tolerated without dose limiting toxicities.
Within 30 minutes of mupadolimab intravenous infusion, a reduction in B cells in blood was seen, consistent with redistribution of B cells to lymphoid tissues.
Corvus presented updated preclinical data characterizing mupadolimab’s dual mechanism of action: Mupadolimab is an IgG1 humanized antibody that has been engineered to be Fc gamma receptor binding deficient. Lab data demonstrated that it completely blocks adenosine production from AMP without a hook effect, which is a reduction in binding with higher concentrations of antibody that may limit efficacy to a narrow range of concentrations. In vitro studies showed that binding of mupadolimab to B cells stimulates activation and differentiation into plasmablasts (antibody producing cells) in a mechanism that is independent of adenosine. In vitro studies showed that T cell functions are inhibited by adenosine monophosphate (AMP) and restored by the addition of mupadolimab.
Corvus analyzed CD73 expression in tumor biopsies, obtained from outside sources, using immunohistochemistry from 75 patients with NSCLC and 31 patients with HNSCC. High CD73 expression was seen in tumor cells and/or stroma in all patients. In HNSCC, CD73 expression is predominantly stromal.
Corvus is also developing mupadolimab as a therapeutic for infectious disease, starting with COVID-19. Preclinical data with humanized mice (mice with human immune system) inoculated with SARS-CoV-2 and influenza viral antigens showed that treatment with mupadolimab enhanced antibody responses that were viral specific, demonstrating its potential to be a universal therapy or adjuvant for viral diseases. In September, Corvus announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. Due to the small sample size, the results did not reach statistical significance. No drug related adverse events were reported in the trial.

Conference Call, Webcast and Presentation Slides
Corvus will host a conference call and webcast today, November 12, 2021, at 9:00 a.m. ET (6:00 a.m. PT), to discuss the update on mupadolimab and other topics. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) and using the conference ID 13724618. The live webcast, which will include presentation slides, may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On November 12, 2021 Greenwich LifeSciences Presented the Corporate Presentation (Presentation, Greenwich LifeSciences, NOV 12, 2021, View Source [SID1234595326]).

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