On November 12, 2021 Checkmate Pharmaceuticals, Inc. (Nasdaq: CMPI) ("Checkmate"), a clinical stage biopharmaceutical company focused on developing its proprietary technology to harness the power of the immune system to combat cancer, reported third quarter 2021 financial results and provided a business update (Press release, Checkmate Pharmaceuticals, NOV 12, 2021, View Source [SID1234595388]).

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"We are excited about the future of vidutolimod as a potential novel treatment for multiple tumor types, including melanoma and head and neck cancer. We continue to advance our clinical trials towards potential data readouts in 2022," said Alan Fuhrman, interim President and Chief Executive Officer of Checkmate.

Recent Business Updates

During The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, Dr. John Kirkwood from the University of Pittsburgh Medical Center presented a poster on the final clinical data from the Phase 1b study of vidutolimod in combination with pembrolizumab or as a monotherapy in patients with anti-PD-1 refractory melanoma.
Vidutolimod in combination with pembrolizumab led to an ORR of 23.5% by RECIST v1.1, a complete response rate of 7.1%, and a median duration of response of 25.2 months.
Vidutolimod monotherapy resulted in a 20.0% ORR by RECIST v1.1 and a median duration of response of 5.6 months.
The most frequent treatment-related adverse events were consistent with flu-like symptoms and injection site reactions and were most commonly Grade 1 or 2.
We appointed Alan Fuhrman, an experienced biotech executive and Checkmate board member, as interim President and CEO.
Ongoing patient recruitment activities and enrollment across our clinical trials evaluating vidutolimod, including:
A Phase 2 trial of vidutolimod in combination with nivolumab in anti-PD-1 refractory advanced melanoma, supported by a clinical collaboration with Bristol Myers Squibb.
A randomized Phase 2/3 trial of vidutolimod in combination with nivolumab vs. nivolumab monotherapy in first-line metastatic or unresectable melanoma, also supported by the clinical collaboration with Bristol Myers Squibb.
A Phase 2 trial of vidutolimod in combination with pembrolizumab in recurrent or metastatic squamous cell head and neck cancer.
Start-up activities underway for the planned expansion of the development program for vidutolimod in combination with cemiplimab in cutaneous squamous cell carcinoma and Merkel cell carcinoma, supported by a clinical collaboration with Regeneron.
Third Quarter 2021 Financial Results

Research and development expenses (R&D): R&D expenses for the three months ending September 30, 2021, were $11.4 million, compared to $6.7 million for the same period in the prior year. This increase reflects higher third-party CRO and manufacturing costs directly related to the vidutolimod clinical trials, in addition to higher personnel and operating expense for the planning and execution of the clinical trials.
General and administration expenses (G&A): G&A expenses for the three months ending September 30, 2021, were $3.6 million, compared to $3.2 million for the same period in the prior year. This increase was primarily attributable to increases in personnel and operating expense incurred in connection with Checkmate operating as a publicly traded company.
Cash, cash equivalents and investments: Cash, cash equivalents and available-for-sale investments were $80.8 million as of September 30, 2021.

On November 12, 2021 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported that a poster presentation describing the adaptive Phase 1/2 trial of LYT-200 for the potential treatment of difficult-to-treat solid tumors will be given at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th annual meeting (Press release, PureTech Health, NOV 12, 2021, View Source [SID1234595405]).

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The scientific poster to be presented at SITC (Free SITC Whitepaper) details the Company’s adaptive Phase 1/2 clinical trial of LYT-200, an investigational monoclonal antibody targeting galectin-9, which is an immunosuppressive protein prominently expressed in multiple difficult-to-treat cancers, including, but not limited to, pancreatic cancer, cholangiocarcinoma, and breast cancer. The clinical study includes a dose finding/dose escalation phase (part 1) and an expansion cohort phase (part 2) in patients with relapsed and refractory metastatic solid tumors. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumor activity of LYT-200 both as a single agent and in combination with either BeiGene’s tislelizumab or chemotherapy. Topline results from the Phase 1 portion of the study are now expected in the first half of 2022 to allow for continued dose escalation as a maximum tolerated dose has not yet been reached.

"PureTech’s preclinical data package elegantly supports the significance of galectin-9 as a therapeutic target, showing it is a multifaceted immunosuppressor in cancer biology and potential biomarker of prognosis," said Zev Wainberg, M.D., Professor of Medicine at UCLA and Co-director of the UCLA GI Oncology Program and the lead primary investigator of the study.

"High galectin-9 levels in patients have been associated with a worse prognosis, and our anti-galectin-9 research candidates outperformed approved immunotherapies in multiple preclinical models of difficult-to-treat cancers, giving us confidence as we moved into the clinical phase to establish key safety and therapeutic parameters and initial insights into efficacy," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech.

Part 1 is a dose-finding study being conducted using a reassessment method to evaluate safety and establish the recommended Phase 2 dose. Two to six patients per treatment cohort are assigned to receive sequentially higher intravenous infusions of LYT-200 every two weeks on day one and day 15 of each 28-day cycle, starting at a dose of 0.2 mg/kg, with escalating dose cohorts up to 16 mg/kg. Part 1 will be completed when six consecutive patients have received the optimal biologic dose and/or the maximal tolerated dose. The study is currently evaluating patients enrolled in the fourth cohort of part 1 at an active dose measuring 6.3 mg/kg. The Phase 2 portion of the study is currently planned to enroll patients with a range of solid tumor types, including pancreatic cancer and other GI solid tumor types.

The U.S. Food and Drug Administration (FDA) recently granted orphan drug designation for LYT-200 for the treatment of pancreatic cancer. The FDA grants orphan drug designation to novel drug and biologic products for the treatment, diagnosis or prevention of conditions affecting fewer than 200,000 persons in the U.S. Orphan drug designation qualifies PureTech for incentives under the Orphan Drug Act, including tax credits for some clinical trials and eligibility for seven years of market exclusivity in the U.S. if the drug is approved.

About LYT-200

LYT-200 is a fully human IgG4 monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial, and results from the Phase 1 portion of the dose escalation trial are expected in the first half of 2022.

On November 12, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported a poster with preclinical data on its TriTAC-XR T cell engager platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Washington, D.C (Press release, Harpoon Therapeutics, NOV 12, 2021, View Source [SID1234595443]).

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The poster, titled "TriTAC-XR is an extended-release T cell engager platform designed to minimize cytokine release syndrome (CRS) by reducing Cmax in systemic circulation," showcased preclinical data supporting the novel platform. The platform is designed to minimize on-target cytokine release syndrome, a hallmark of many T cell engagers that can lead to dose limiting toxicities.

Studies in non-human primates with FLT3-targeting T cell engagers confirmed that the slow build-up of active drug and the reduction of differences in peak-to-trough drug concentrations can reduce CRS and improve the safety of T cell engagers. Importantly, the reduction of cytokine release could be achieved while maintaining efficacy in in vivo models. When compared to a TriTAC with the same three binding domains, the TriTAC-XR was able to deplete FLT3-expressing cells with comparable potency despite a 100x reduction in cytokines in cynomolgus monkeys.

"These encouraging data demonstrate that our TriTAC-XR T cell engager platform has the potential to meaningfully mitigate CRS, and we intend to explore if this approach enables the use of T cell engagers for the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies," said Holger Wesche, Ph.D., Chief Scientific Officer of Harpoon Therapeutics.

"The introduction of TriTAC-XR represents the third T cell engager platform and the second protease-activated T cell engager prodrug platform from Harpoon. This further showcases the productivity and creativity of our research efforts, and our commitment to the development of best-in-class T cell engagers," said Julie Eastland, Chief Executive Officer of Harpoon Therapeutics.

Harpoon’s first platform, the constitutively active TriTAC, is designed to minimize off-target toxicities, and is ideal for targets with limited on-target liabilities. The ProTriTAC platform offers similar advantages with activation directed primarily to the tumor microenvironment. This spatial control of activation may address on-target tissue damage, hence enabling an expansion of the T cell engager target space. The TriTAC-XR now adds improved temporal control and is designed to be activated in the systemic circulation at a predefined rate to minimize on-target CRS.

Preclinical data from the TriTAC platform demonstrated:

TriTAC-XR is an extended-release T cell engager platform designed to mitigate cytokine release syndrome by releasing active T cell engagers from an inactive prodrug in a temporally controlled fashion, thus avoiding the very high exposures (Cmax) that occur shortly after administration with constitutively active molecules.
A single dose of FLT3 TriTAC-XR produced similar PD effects with significantly lower cytokines than a comparable TriTAC in non-human primate animal models.
The expected safety improvement of TriTAC-XR could enable the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies.

On November 12, 2021 Asher Biotherapeutics, a biotechnology company developing precisely-directed immunotherapies for cancer, autoimmune, and infectious diseases, reported new preclinical data demonstrating proof of concept for its cis-targeting platform and lead program AB248 (Press release, Asher Biotherapeutics, NOV 12, 2021, View Source [SID1234595460]). AB248 is an engineered intereukin-2 (IL-2) immunotherapy, designed to selectively target CD8+ effector T cells. The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (SITC 2021), being held in Washington D.C. and virtually, November 10-14, 2021.

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"We are pleased to share two presentations at SITC (Free SITC Whitepaper), providing further evidence that our cis-targeting approach enables us to craft exquisitely selective molecules, which activate only the desired immune cell types. This approach allows us to deliver immune activators to the cell types that drive efficacy, while avoiding other cell types that can lead to increased toxicities or other undesired consequences. These data provide further validation for our platform, which has now generated multiple lead molecules against high value targets and support our efforts to advance a pipeline of immunotherapies to provide better outcomes to patients," said Andy Yeung, Ph.D., Chief Technology Officer and Founder of Asher Bio.

Ivana Djuretic, Ph.D., Chief Scientific Officer and Founder of Asher Bio, added: "Historically IL-2 has proven to be a very potent immunotherapy capable of inducing durable complete responses in some cancer patients, but IL-2’s potential has been severely limited by toxicities, which arise due to non-selective activation of many different cell types. Our approach is to focus IL-2 to selectively activate CD8+ T cells, the primary immune cell subset that drives anti-tumor efficacy in response to IL-2 pathway activation. We are encouraged by the preclinical results presented at SITC (Free SITC Whitepaper), which demonstrate the potential for AB248 to deliver both enhanced anti-tumor efficacy and improved safety and reinforce our confidence in AB248’s potential as a best-in-class IL-2 immunotherapy. We look forward to advancing AB248 into clinical studies across multiple solid tumor types next year."

In an oral presentation titled, "CD8-targeted IL-2 drives potent anti-tumor efficacy and promotes action of tumor specific vaccines," Bob Schreiber, Ph.D., Professor of Pathology & Immunology; Director, Bursky Center for Human Immunology & Immunotherapy Programs; Washington University School of Medicine and a scientific founder of Asher Bio, reviewed new preclinical data from studies of CD8-IL2, a murine surrogate of AB248, which was evaluated in a T3 sarcoma model. The data showed that:

In an anti-PD-1 resistant tumor model, a single dose of CD8-IL2 resulted in complete tumor rejection in 90% of treated mice. In contrast, high dose IL-2 produced minimal efficacy.
Treatment with CD8-IL2 led to the expansion of antigen specific T cells with increased expression of activation-associated markers and reduced expression of exhaustion-associated markers.
CD8-IL2 monotherapy was well-tolerated, demonstrating therapeutic activity without inducing body weight loss.
In a poster titled, "Selective activation of CD8+ T cells by a CD8-targeted IL-2 results in enhanced anti-tumor efficacy and safety," lead author Kelly Moynihan, Ph.D., Associate Director and AB248 Program Lead at Asher Bio, described the design of ­cis-targeted CD8-IL2 molecules and reviewed preclinical in vitro and in vivo data, which showed that:

Treatment with a single dose of CD8-IL2 resulted in a majority of complete responses in established MC-38 tumors, and superior efficacy as compared to a "not α" IL-2. CD8-IL2 also showed marked synergy in combination with an anti-PD1 against established B16F10 melanomas, inducing complete responses in 100% of treated mice.
Efficacy with a "not α" IL-2 in mice cannot be achieved unless "not α" IL-2 is dosed to levels that drive a high degree of toxicity-induced body weight loss (>10%). In contrast, treatment with CD8-IL2 drives strong anti-tumor efficacy without inducing body weight loss.
Treatment with CD8-IL2 led to selective expansion of CD8+ T cells in both the peripheral blood and tumor compartments in mice, and in cynomolgus monkeys, showed strong and selective expansion of CD8+ T cells.
Both presentations will be available in the "Presentations and Posters" section of Asher Bio’s website: View Source

On November 12, 2021 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), is a U.S. biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported financial results for the third quarter of 2021 (Press release, CASI Pharmaceuticals, NOV 12, 2021, View Source [SID1234595492]).

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Wei-Wu He, Ph.D., CASI’s Chairman and Chief Executive Officer, commented, "We are pleased to report $8.1 million in EVOMELA revenues for the quarter. We remain confident in our guidance for our full-year 2021 revenue growth to exceed 2020 revenues by over 80%. This continued growth further demonstrates our 100+ person sales and marketing team’s ability to cover all major hospitals and key multiple myeloma transplant physicians. We look forward to leveraging this success in the anticipated launch of our next product, Juventas’ CNCT-19, which our partner announced has officially entered phase II of a registered clinical trial, and other products."

Dr. He continued, "Our partner BioInvent announced additional positive, interim top-line data from the Phase 1/2a clinical trial of its novel anti-FcγRIIB antibody BI-1206 in combination with rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with indolent relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). BI-1206, in combination with rituximab, demonstrated an objective response rate (ORR) of 50%, with three complete responses and three partial responses seen in twelve patients evaluated for therapeutic benefit. The treatment stabilized the disease in one additional patient, giving a disease control rate of 58% (7 out of 12 patients). We believe BI-1206 has potential application across multiple tumor types in both first-line treatments and relapsed/refractory settings. Additionally, our CNCT-19 CAR-T partner, Juventas, completed a Series C financing round through which it raised more than RMB410 million (approximately $63 million USD). CASI has a 12.01% ownership stake in Juventas and shares global co-commercial and profit-sharing rights for CNCT-19 with Juventas. We believe this financing will allow Juventas to continue the rapid development and registration of CNCT-19 in China. Overall, we are pleased with our momentum and will continue to execute on key milestones across our broad portfolio in the quarters ahead."

Third Quarter 2021 Financial Results

Revenues consist of product sales of EVOMELA that launched during August 2019. Revenue was $8.1 million for the three months ended September 30, 2021 compared to $4.2 million for the three months ended September 30, 2020. Revenues increased by 93% in the third quarter of 2021 as compared to same quarter in 2020 due to the continued strong growth in EVOMELA sales.

Costs of revenues were $3.4 million for the three months ended September 30, 2021, compared to $1.8 million for the three months ended September 30, 2020, which includes royalty payment of $1.6 million and $0.8 million for the same period. Costs of revenues excluding royalty were $1.8 million and $1.0 million for the three months ended September 30, 2021, and 2020. Costs of revenues, excluding royalty as a percentage of revenues, decreased significantly in the three months ended September 30, 2021, compared within the three months ended September 30, 2020, due to the alternate manufacturer in place, resulting in a considerable decrease in the unit cost of inventories of EVOMELA.

General and administrative expenses for the three months ended September 30, 2021 were $5.3 million, compared with $5.3 million for the three months ended September 30, 2020.

Selling and marketing expenses for the three months ended September 30, 2021 were $3.4 million, compared with $2.1 million for the three months ended September 30, 2020. The increase in selling and marketing expenses was due to expansion of sales team in China in 2021.

R&D expenses for the three months ended September 30, 2021 were $2.9 million, compared to $2.8 million for the three months ended September 30, 2020.

Net loss for the three months ended September 30, 2021 was $10 million compared to $16.7 million for the three months ended September 30, 2020 due to the increase in revenues. As of September 30, 2021, CASI had cash and cash equivalents of $53.1 million compared to $57.1 million as of December 31, 2020.
Further information regarding the Company, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, can be found at www.casipharmaceuticals.com.

Conference Call

The conference call can be accessed by dialing 1-877-870-4263 (U.S.) or 1-412-317-0790 (international) and ask to be joined into the CASI Pharmaceuticals call to listen to the live conference call.

This call will be recorded and available for replay by dialing 1-877-344-7529 (U.S.) or 1-412-317-0088 (international) and enter 10160251 to access the replay.