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OSE Immunotherapeutics Announces: Positive Phase 3 Data from its Cancer Vaccine in Lung Cancer Patients with Resistance to Previous Immunotherapy Published in Annals of Oncology

On September 11, 2023 OSE Immunotherapeutics SA reported the peer-reviewed publication in Annals of Oncology* of the randomized Phase 3 clinical trial (Atalante-1**) on T-cell epitope cancer vaccine Tedopi in HLA-A2 positive patients with advanced or metastatic NSCLC in monotherapy in third line NSCLC with secondary resistance to immune checkpoint inhibitors (ICI) (Press release, OSE Immunotherapeutics, SEP 11, 2023, View Source [SID1234635083]).

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Tedopi is a novel T-cell epitope-based cancer vaccine targeting five tumor-associated antigens, an activating and differentiated off-the-shelf immunotherapy expanding tumor specific T-lymphocytes in HLA-A2 cancer patients. The article, titled "Randomized Open-Label Controlled Study of Cancer Vaccine OSE2101 Versus Chemotherapy in HLA-A2-positive Patients with Advanced Non-Small Cell Lung Cancer with Resistance to Immunotherapy: ATALANTE-1" features positive data from the randomized international Phase 3 study showing that novel cancer vaccine Tedopi improves overall survival with a better safety and quality of life profile in monotherapy compared to chemotherapy in HLA-A2 positive patients with advanced or metastatic NSCLC who have progressed at least 12 weeks after sequential treatment with chemotherapy and immune checkpoint inhibitors (ICI).

Prof. Benjamin Besse, Director of Clinical Research at Gustave Roussy Institute (IGR, Villejuif, France), and Principal Investigator of the Atalante-1 clinical trial, commented: "Tedopi is the first cancer vaccine to demonstrate positive results on survival in a randomized Phase 3 trial in advanced and metastatic NSCLC cancer patients in 3rd line. A significant reduction of the risk of death by 41% was achieved with a better safety profile and a maintained quality of life. This study, conducted in patients with secondary resistance to immunotherapy, compared Tedopi monotherapy with standard of care docetaxel or pemetrexed chemotherapies. Further evaluation is clearly warranted in a second line of treatment of advanced and metastatic NSCLC, to potentially make this cancer vaccine available to hard-to-treat patients in failure and with high medical needs."

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: "Tedopi is the most advanced therapeutic cancer vaccine in clinical development. These Phase 3 data, demonstrating the promising effects, have now been validated in the internationally recognized journal ‘Annals of Oncology’, a major achievement for all involved so, in particular, we’d like to thank warmly the investigators, the patients and their families for their commitment. This Phase 3 positive monotherapy data and moreover the recently announced positive Phase 1 and 2 results using other personalized cancer vaccines in combination to treat resected melanoma or pancreatic cancer patients, highlight the promise of this new therapeutic class of vaccines. The clinical value of our results, re-activating specifically the anti-tumor immune responses, is particularly interesting in patients showing immune escape from checkpoint inhibitors. The confirmatory pivotal Phase 3 trial in preparation (first patient expected early 2024) is planned to support the regulatory registration of Tedopi in secondary resistance to immune checkpoint inhibitors, this time in second line NSCLC treatment."

Main results of the first Phase 3 clinical trial of Tedopi in HLA-A2+ patients with NSCLC

This Phase 3 clinical trial has demonstrated a significant therapeutic benefit in patients with secondary

resistance (1) to immune checkpoint inhibitors (ICI) defined as patients with failure to platinum-based chemotherapy followed by a minimum of 12 weeks ICI treatment (main analysis of the trial). Tedopi demonstrated a favorable benefit/risk ratio versus standard of care (SoC) docetaxel or pemetrexed in advanced HLA-A2+ NSCLC patients with secondary resistance to ICI.

The main results were:

Improved efficacy

1. Overall survival (primary endpoint) was statistically significantly improved for Tedopi:
HR=0.59 (95% CI: 0.38, 0.91) in favor of the Tedopi arm, reduced risk of death by 41%.
44.4% overall survival rate at 1 year with Tedopi versus 27.5% with chemotherapy. A clinically meaningful gain in median overall survival of 3.6 months in favor of the Tedopi arm with Tedopi OS at 11.1 months versus 7.5 months for SoC (p=0.017).

2. Post progression survival was also significantly longer in the Tedopi arm (7.7 months versus 4.6 months; p=0.004, HR=0.46).

Improved safety profile and Quality of Life

The ECOG performance status(2), of maintained general health condition with time to ECOG deterioration was significantly longer in the Tedopi arm (9.0 months versus 3.3 months; p=0.006; HR=0.43).
A better quality of life was observed with Tedopi (p= 0.04). (Global health status: p=0.045; Role Functioning: p=0.025).
A good tolerance profile of Tedopi with fewer Severe Adverse Events grade 3-5 (Tedopi 38% vs SoC 68%, p<0.001). No Treatment Emergent Adverse Effects of concern in the Tedopi arm.
(1) Secondary resistance is defined as failure after a minimum of 12 weeks of Immune checkpoint inhibitor given in sequential chemotherapy – checkpoint inhibitors treatment (Kluger HM et al; Journal for immunoTherapy of Cancer 2020 Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC (Free SITC Whitepaper) Immunotherapy Resistance Taskforce)
(2) The ECOG score is a performance scale used to quantify the general health condition of a patient. It is subdivided into 5 grades from 0 to 5, ranging from fully active (0) to fully disabled, then to death (5).

ABOUT OSE Immunotherapeutics

OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology and immuno-inflammation.

The Company’s current well-balanced first-in-class clinical pipeline includes:

Tedopi (immunotherapy activating tumor specific T-cells, off-the-shelf, neoepitope-based): this cancer vaccine is the Company’s most advanced product; positive results from the Phase 3 trial (Atalante 1) in Non-Small Cell Lung Cancer patients in secondary resistance after checkpoint inhibitor failure. Other Phase 2 trials, sponsored by clinical oncology groups, of Tedopi in combination are ongoing in solid tumors.
OSE-279 (anti-PD1): ongoing Phase 1/2 in solid tumors or lymphomas (first patient included). OSE-279 is the backbone therapy of the BiCKI platform.
OSE-127 – lusvertikimab (humanized monoclonal antibody antagonist of IL-7 receptor); ongoing Phase 2 in Ulcerative Colitis (sponsor OSE Immunotherapeutics); ongoing preclinical research in leukemia (OSE Immunotherapeutics).
FR-104/VEL-101 (anti-CD28 monoclonal antibody): developed in partnership with Veloxis Pharmaceuticals, Inc. in transplantation; ongoing Phase 1/2 in renal transplant (sponsor Nantes University Hospital); Phase 1 ongoing in the US (sponsor Veloxis Pharmaceuticals, Inc.).
OSE-172/BI 765063 (anti-SIRPα monoclonal antibody on CD47/SIRPα pathway) developed in partnership with Boehringer Ingelheim in advanced solid tumors; positive Phase 1 dose escalation results in monotherapy and in combination, in particular with anti-PD-1 antibody ezabenlimab; international Phase 1b ongoing clinical trial in combination with ezabenlimab alone or with other drugs in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC).
OSE Immunotherapeutics expects to generate further significant value from its two proprietary drug discovery platforms, which are central to its ambitious goal to deliver next-generation first-in-class immunotherapies:

BiCKI platform focused on immuno-oncology (IO) is a bispecific fusion protein platform built on the key backbone component of anti-PD1 combined with a new immunotherapy target to increase anti-tumor efficacy. BiCKI-IL-7 is the most advanced BiCKI candidate targeting anti-PD1xIL-7.
Myeloid platform focused on optimizing the therapeutic potential of myeloid cells in IO and immuno-inflammation (I&I). OSE-230 (ChemR23 agonist mAb) is the most advanced candidate generated by the platform, with the potential to resolve chronic inflammation by driving affected tissues to tissue integrity.

CymaBay Announces Pricing of Upsized $225 Million Public Offering of Common Stock and Pre-Funded Warrants

On September 11, 2023 CymaBay Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing innovative therapies for liver and other chronic diseases with high unmet medical need, reported the pricing of its previously announced underwritten public offering of common stock and pre-funded warrants (Press release, CymaBay Therapeutics, SEP 11, 2023, View Source [SID1234635081]). CymaBay is selling 12,551,080 shares of common stock and, in lieu of common stock to certain investors, pre-funded warrants to purchase 583,771 shares of common stock in the offering. The shares of common stock are being sold at a public offering price of $17.13 per share, and the pre-funded warrants are being sold at a public offering price of $17.1299 per underlying share. The gross offering proceeds to CymaBay from this offering are expected to be approximately $225 million, before deducting the underwriting discount and other estimated offering expenses, and excluding the exercise of any pre-funded warrants. The pre-funded warrant has an exercise price of $0.0001 per share. All shares of common stock and pre-funded warrants to be sold in the offering are being offered by CymaBay. CymaBay has granted the underwriters a 30-day option to purchase up to an additional 1,970,227 shares of its common stock at the public offering price per share less underwriting discounts and commissions. The offering is expected to close on September 14, 2023, subject to the satisfaction of customary closing conditions.

CymaBay anticipates using the net proceeds from the offering to fund ongoing development of seladelpar, including clinical trials targeting market expansion, and for working capital and general corporate purposes.

Piper Sandler, Raymond James, Cantor and LifeSci Capital are acting as the joint book-running managers for the offering. BTIG is acting as the lead manager for the offering.

The securities described above are being offered by CymaBay pursuant to a shelf registration statement filed with the Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement and accompanying prospectus related to the offering has been filed, and a final prospectus supplement and accompanying prospectus related to the offering will be filed, with the SEC and are or will be available on the SEC’s website at www.sec.gov. Copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained, when available, from: Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by telephone at (800) 747-3924, or by email at [email protected]; Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by e-mail at [email protected]; or LifeSci Capital LLC, Attention: Syndicate Prospectus Department, 250 West 55th Street, 34th Floor, New York, NY 10019, by email at [email protected] or by telephone at (646) 876-5059.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

PeproMene Bio, Inc. Announced Completion of the First Dose Cohort and Opening of the Second Dose Cohort in Its B-cell Non-Hodgkin Lymphoma (B-NHL) Phase 1 Clinical Trial of PMB-CT01 (BAFFR-CAR T Cells)

On September 11, 2023 PeproMene Bio, Inc., a clinical-stage biotech company developing novel therapies to treat cancers and immune disorders, reported that the first dose cohort of its phase 1 relapsed or refractory B-cell Non-Hodgkin Lymphoma (r/r B-NHL) clinical trial of PMB-CT01 (BAFFR-CAR T Cells) has been completed (Press release, PeproMene Bio, SEP 11, 2023, View Source [SID1234635080]). No Dose Limiting Toxicity (DLT) was observed, and the study has been cleared to proceed with the next cohort.

The PMB-102 trial is taking place at City of Hope, one of the largest cancer research and treatment organizations in the nation. PeproMene licensed intellectual property relating to PMB-CT01 from City of Hope, which developed the therapy.

In the first cohort, administration of 50×106 PMB-CT01 has been extremely well tolerated. Among three treated patients, all three experienced only grade 1 cytokine release syndrome ("CRS") and two had grade 1 immune effector cell-associated neurotoxicity syndrome ("ICANS") with full recovery. The Overall Response Rate is 100% (two Complete Response and one Partial Response) at one-month post treatment. Two patients with mantle cell lymphoma had progressed after conventional CD19 CAR T-cell treatment prior to enrollment on PMB-CT01.

"We are pleasantly surprised and thrilled to see such minimal toxicity associated with such a high response rate in heavily pretreated patients who have failed 3-10 prior lines of therapy, including FDA-approved CD19 CAR T-cells", said Elizabeth Budde, M.D., Ph.D., the principal investigator of this single-center, dose escalation trial (NCT05370430) and associate professor at City of Hope, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation.

"Despite high initial efficacy of CD19-CAR T cell therapy for B-cell lymphoma and leukemia, a significant number of patients still relapse after CD19-CAR T treatment, highlighting the urgent unmet medical need," said Larry W. Kwak, M.D., Ph.D., vice president and deputy director of City of Hope’s Comprehensive Cancer Center and PeproMene’s scientific founder and compensated chair of its Scientific Advisory Board. Kwak has an equity interest in PeproMene. "Unlike CD19, BAFF-R signaling is required for B cell growth and survival, so it may limit the capacity of B cell tumors to evade therapy by loss of BAFF-R expression. I hope BAFFR-CAR T therapy will offer a clinically meaningful, new option for patients."

"Although still in early stage, we are encouraged by the initial observation of acceptable safety and preliminary efficacy in the first dose cohort of PMB-CT01 treated B-NHL patients. All 3 treated patients (2 progressed after CD19 CAR T therapy and 1 with CD19/CD20 negative lymphoma) responded to PMB-CT01 treatment," said Hazel Cheng, Ph.D., COO of PeproMene. "These clinical outcomes are consistent with City of Hope preclinical research data published in Science Translational Medicine in 2019, which showed that PMB-CT01 (BAFFR-CAR T Cells) could overcome CD19 antigen loss in B-cell malignancies."

About PMB-CT01

PMB-CT01 is a first-in-class BAFFR-targeted, autologous CAR T cell therapy. BAFF-R (B Cell Activating Factor Receptor), a tumor necrosis factor (TNF) receptor superfamily member, is the main receptor for BAFF expressing almost exclusively on B cells. Since BAFF-R signaling promotes normal B-cell proliferation and appears to be required for B-cell survival, it is unlikely tumor cells could escape immune responses via loss of BAFF-R antigen. This unique characteristic makes BAFF-R CAR T therapy a great potential treatment of B cell malignancies. BAFF-R CAR-T was constructed using the anti-BAFF-R scFv (single-chain fragment variable) antibodies with the 2nd generation signaling domains containing CD3ζ and 4-1BB. Our research has found that BAFFR-CAR T cells kill human lymphomas and leukemias in vitro as well as in animal models. PeproMene has licensed intellectual property relating to PMB-CT01, from City of Hope.

Medivir’s Partner Tango Therapeutics received FDA clearance to start the TNG348 phase 1/2 clinical study

On September 11, 2023 Medivir AB (NASDAQ Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that Medivir’s partner Tango Therapeutics has received FDA clearance on its Investigational New Drug application for TNG348 (Press release, Medivir, SEP 11, 2023, View Source [SID1234635078]).

TNG348 is a novel USP1 (ubiquitin-specific protease 1) inhibitor for the treatment of BRCA1/2-mutant and other homologous recombination deficiency (HRD)+ cancers. HRD+ cancers, including BRCA1/2 mutations, represent up to 50% of ovarian cancers, 25% of breast cancers, 10% of prostate cancers and 5% of pancreatic cancers.

Tango Therapeutics intends to initiate a phase 1 / 2 study with TNG348 in first half of 2024, both as single agent and in combination with a PARP-inhibitor. Preclinical data has shown synergistic effect with PARP inhibitors in PARP naïve models and that TNG348 is active in models with resistance to PARP inhibitors. These data suggest that TNG348 may benefit patients both as single agent or in combination with PARP inhibitors.

TNG348 is a USP-1 inhibitor developed from the preclinical USP-1 program in-licensed from Medivir in 2020.

Under the licensing agreement, Medivir is entitled to multiple development and commercial milestone payments as well as royalties on future sales.

"It is very encouraging to see another preclinical molecule developed by Medivir being evaluated in patients. The preclinical data generated by Tango Therapeutics looks very promising and we will be following the clinical development of TNG348 with great anticipation," says Jens Lindberg, CEO of Medivir.

For additional information, please contact;
Magnus Christensen, CFO, Medivir AB
Telephone: +46 8 5468 3100. E-mail: [email protected]

IDEAYA Announces Phase 1 Expansion and Preliminary Clinical Proof-of-Concept for Potential First-in-Class PARG Inhibitor IDE161 in HRD Solid Tumors

On September 11, 2023 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported initiation of a Phase 1 monotherapy expansion in the first-in-human clinical trial evaluating IDE161 (NCT 05787587) (Press release, Ideaya Biosciences, SEP 11, 2023, View Source [SID1234635077]).

"We are pleased to advance IDE161, a potential first-in-class PARG inhibitor, into an expansion phase of our Phase 1 clinical trial and are excited to explore its potential in cancer patients with homologous recombination deficiency (HRD). Based on extensive preclinical studies, we are focusing this expansion in several priority tumor types, including ER+, Her2(-) breast cancer and ovarian cancer subjects with tumors that harbor HRD," said Dr. Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"The clinical update today on IDE161 represents the first reported preliminary clinical proof-of-concept for a PARG inhibitor in HRD solid tumors. We look forward to the continued evaluation of IDE161 as a monotherapy in high unmet medical need HRD solid tumor indications," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences.

The Phase 1 first-in-human clinical trial is evaluating the safety, tolerability, pharmacokinetic and pharmacodynamic properties and preliminary efficacy of IDE161 in patients having tumors with homologous recombination deficiency (HRD). Early clinical data from the dose escalation cohorts showed dose-dependent pharmacodynamic modulation of poly-ADP ribose (PAR) proteins in peripheral blood, demonstrating IDE161 target engagement. These clinical data also demonstrated IDE161 exposure levels in humans which correlate to preclinical exposures that were efficacious, achieving tumor regressions in xenograft models.

The Phase 1 expansion is based on preliminary tumor shrinkage observed in multiple HRD solid tumor patients, including an BRCA1/2 endometrial cancer subject with a first imaging assessment of a partial response in the target lesion, a complete response in the non-target lesion and an 87% reduction in the CA-125 tumor marker (2,638 units/ml at baseline to 360 units/ml at 6-weeks). The company is also continuing to evaluate the optimal move forward dose for Phase 2 expansion. The expansion portion of the Phase 1 trial will include patients having HRD-associated breast cancer and ovarian cancer, as well as a basket of other selected solid tumors. The breast cancer focus is on estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (Her2-), HRD+ tumors, which represent approximately 10% to 14% of breast cancer patients. The ovarian cancer focus represents approximately 50% of ovarian cancer where HRD is observed. IDEAYA is targeting clinical program updates for IDE161 in the second half of 2023.

IDE161 is a potent, selective, small-molecule inhibitor of PARG, a novel and mechanistically-differentiated target in the same clinically validated pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA presented a poster with preclinical data profiling IDE161 at the 2023 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in April 2023. The IDE161 poster is available online at the company’s website at View Source

IDEAYA owns or controls all commercial rights in IDE161, subject to certain economic obligations under its exclusive, worldwide license with Cancer Research UK and University of Manchester.