On November 11, 2022 Avstera Therapeutics Corp, an oncology-focused biotech dedicated to address the large disease burden and significant unmet need of cancer patients, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Avstera’s AVS100 compound, which is a highly specific HDAC6 inhibitor, for the treatment of stage IIB through IV melanoma (Press release, Avstera Therapeutics, NOV 11, 2022, View Source [SID1234623856]).

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AVS100 is a novel highly specific HDAC6 inhibitor with unique mechanisms in its ability to polarize macrophages to the anti-tumoral M1 phenotype. Macrophage differentiation and stabilization of M1 is a key element in maintaining overall anticancer responses. AVS100 has been shown to significantly reduce tumor growth and improve overall survival in preclinical animal models. AVS100 remains on track for planned IND filing next year targeting locally advanced or metastatic solid tumors, including melanoma.

"The FDA’s grant of this ODD for AVS100 highlights the significant unmet need there remains for this patient population and the impact our therapy can have in potentially improving clinical outcomes. Advanced stage melanoma remains a complex and difficult cancer to treat with current approaches, and AVS100 has the potential to provide an opportunity to potentially reduce the disease burden shared by these patients." added Karthik Musunuri, CEO & Co-Founder of Avstera Therapeutics Corp.

The research behind the HDAC6 inhibitor technology stems from Alejandro Villagra’s lab at Georgetown; through licenses made with the George Washington University.

"The use of selective HDAC6i treatment is an exciting approach to manipulate the tumor microenvironment and prime the host to increase the therapeutic response to checkpoint inhibitor therapy. This provides hope to patients who may have progressed on single agent treatment and are looking to boost response, or those unable to tolerate dual immunotherapy for refractory or more advanced cases." added Vishal Patel, MD, FAAD, FACMS, Director of the Cutaneous Oncology Program at the George Washington Cancer Center and Member of Avstera’s SAB.

The FDA Office of Orphan Products Development grants orphan designation for novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 patients in the U.S. Orphan designation qualifies the sponsor of the drug for various development incentives of the Orphan Drug Act, including a seven-year period of U.S. marketing exclusivity, tax credits for clinical research costs, clinical research trial design assistance, the ability to apply for annual grant funding and waiver of Prescription Drug User Fee Act filing fees.

On November 11, 2022 – Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that it will effect a 1-for-50 reverse stock split of its outstanding and authorized common stock, effective at 5:00 p.m. (EST) on November 11, 2022 (Press release, Kintara Therapeutics, NOV 11, 2022, View Source [SID1234623855]). Kintara’s common stock will continue to trade on The Nasdaq Capital Market under the symbol "KTRA" and under a new CUSIP number, 49720K200. Kintara’s common stock will begin trading on a reverse stock split-adjusted basis on The Nasdaq Capital Market when the market opens on November 14, 2022.

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The reverse stock split is intended to increase the per share trading price of Kintara’s common stock to satisfy the $1.00 minimum bid price requirement for continued listing on The Nasdaq Capital Market (Nasdaq Listing Rule 5550(a)(2)). As a result of the reverse stock split, every fifty pre-split shares of common stock outstanding and authorized will automatically combine into one new share of common stock without any action on the part of the stockholders. The number of outstanding shares of common stock will be reduced from 80,807,316 shares issued and outstanding as of November 8, 2022, to approximately 1,616,146. The number of authorized shares of common stock will be reduced from 275,000,000 shares authorized, to 5,500,000.

No fractional shares will be issued in connection with the reverse stock split. Any fractional shares of common stock resulting from the reverse stock split will be rounded up to the nearest whole post-split share and no stockholders will receive cash in lieu of fractional shares. The reverse stock split will also apply to common stock issuable upon the conversion of Kintara’s outstanding preferred stock and the exercise of Kintara’s outstanding warrants, restricted stock units, and stock options, with adjustments to the conversion prices and exercise prices thereof as required by the terms of those securities.

No stockholder approval of the reverse stock split was required under Nevada law, and on October 28, 2022, the Board of Directors of the Company approved and authorized the reverse stock split at a ratio of one-for-fifty (1:50).

Mountain Share Transfer, LLC is acting as the exchange agent and transfer agent for the reverse stock split. Stockholders holding their shares in book-entry form or in brokerage accounts need not take any action in connection with the reverse stock split. Beneficial holders are encouraged to contact their bank, broker or custodian with any procedural questions.

On November 11, 2022 OncoSec Medical Incorporated (NASDAQ: ONCS) (the "Company" or "OncoSec"), a clinical-stage biotechnology company developing intratumoral immunotherapies that stimulate the patient’s immune system to target cancer cells and eradicate disease, reported data from the Phase 2 KEYNOTE-695 clinical trial (Press release, OncoSec Medical, NOV 11, 2022, View Source;keytruda-in-patients-with-advanced-melanoma-refractory-to-anti-pd-1-treatment-301675588.html [SID1234623854]). This global, open-label single-arm trial is evaluating TAVO, OncoSec’s proprietary IL-12 encoding plasmid delivered by intratumoral electroporation (TAVO-EP), in combination with pembrolizumab in patients with unresectable or metastatic (Stage III/IV) melanoma who had progressed on immediate prior anti-PD-1 antibody therapy (pembrolizumab or nivolumab). The last patient started treatment in December 2020, and clinical database lock occurred in October 2022.

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The key secondary endpoint of KEYNOTE-695 was met. Investigator assessment of overall response rate (ORR) per RECIST v1.1, from 101 efficacy evaluable patients, with at least one post-baseline tumor assessment, showed a confirmed ORR of 18.8% (95% confidence interval: 11.7, 22.8), which exceeds the pre-specified clinically meaningful ORR of ≥17% (95% CI: 10.2, 25.8).

Three patients achieved a complete response (CR) and 16 patients had a partial response (PR). Of note, 2 patients with CR had discontinued treatment with immediate prior nivolumab/ipilimumab. The disease control rate (CR + PR + stable disease) was 40.6%. The investigator-assessed durable response rate of ≥24 weeks was 15.8%, the median duration of response had not been reached. The median overall survival was 22.7 months (95% CI: 14.4, 35.5) after a median follow-up period of 33.4 months. The trial enrolled and collected safety data on 105 patients who had received at least 12 weeks of anti-PD-1 treatment and had confirmed disease progression. The combination therapy was generally well tolerated with no Grade 4/5 treatment-related adverse events (TRAEs). Grade 3 TRAEs were observed in 4.8% of patients.

Top-line results of the primary endpoint of the KEYNOTE-695 trial, ORR by blinded, independent central review (BICR) based on RECIST v1.1, are expected to be announced in the first quarter of 2023.

"Patients with PD-1 refractory melanoma have limited treatment options. Therefore, we are encouraged by the observed response to treatment with TAVO-EP and pembrolizumab in this difficult to treat patient segment," said Robert Arch, Ph.D., Chief Executive Officer of OncoSec. "In addition to the ORR of 18.8% in the full trial population of KEYNOTE-695, we are intrigued by the observed 19.5% investigator-assessed ORR, including 2 CRs and 6 PRs, in a subset of 41 patients who had prior exposure to ipilimumab (anti-CTLA-4 antibody) in addition to anti-PD-1 therapy. The data of TAVO-EP combination treatment in patients who had failed multiple checkpoint inhibitors is encouraging and speaks to the differentiation of our TAVO-EP approach from checkpoint inhibitors and other immunotherapies. I want to thank all patients who participated in the trial and our team at OncoSec that remains focused on developing TAVO-EP as a novel intratumoral treatment approach for cancer patients with unmet medical needs."

Adil Daud, MD, Professor; UCSF Helen Diller Family Comprehensive Cancer Center commented on the data: "Patients with unresectable advanced melanoma who have progressed on prior anti-PD-1 therapy are not expected to gain benefit from retreatment with anti-PD-1 therapy. Therefore, the KEYNOTE-695 data highlight the value of intratumoral IL-12 as treatment for patients with checkpoint inhibitor refractory melanoma. Importantly, TAVO-EP in combination with pembrolizumab in this highly refractory patient population with no standard-of-care treatment options showed durable responses and good tolerability. These data suggest that TAVO-EP combined anti-PD-1 antibodies could make a major difference for a group of patients with a high unmet medical need."

On November 11, 2022 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of Elite Responders, reported preclinical data on immuno-oncology candidates OR2805 and OR502 presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, OncoResponse, NOV 11, 2022, View Source [SID1234623853]).

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OR2805 is a fully human monoclonal antibody identified from an Elite Responder using OncoResponse’s proprietary B-cell discovery platform. OR502 is a novel humanized antibody to leukocyte immunoglobulin-like receptor-B2 (LILRB2, ILT4) protein.

"Our data presented at SITC (Free SITC Whitepaper) highlight the ability of OR2805 and OR502 to modulate inhibitory macrophages in the tumor microenvironment and induce anti-tumor immune activity. In preclinical models, OR502 restores innate and adaptive immune responses by modulating immunosuppressive myeloid cells and can reverse unresponsiveness to anti-PD-1 treatment," said Kamal Puri, PhD, Chief Scientific Officer of OncoResponse. "These initial, promising data support continued development of these candidates."

"We are pleased to present preclinical scientific data on our pipeline of macrophage-modulating antibodies that support advancement to clinical studies: OR2805 now in Phase 1, and OR502 slated for IND in 2023," said Clifford Stocks, Chief Executive Office of OncoResponse.

Presentation highlights include:

Abstract Number: 39

Interrogating Elite Responder humoral responses to identify novel targets and therapeutic antibodies for the treatment of cancer

OR2805 demonstrates specific binding to immunosuppressive myeloid cells.
M2c macrophages treated with OR2805 promote T-cell activation and proliferation.
OR2805 induces anti-tumor activity in humanized mouse models.
OR2805 amplifies anti-PD-1 activity in M2c/T cell coculture assays demonstrating potential as a single agent or in combination with checkpoint inhibitors.
Interrogation of humoral responses in Elite Responders is an attractive strategy for discovery of novel targets and therapeutic antibodies for the treatment of cancer.
Abstract Number: 498

Preclinical characterization of OR502, an anti-LILRB2 antibody that rescues innate and adaptive immune responses from LILRB2 mediated immune suppression

OR502 demonstrates specific binding to LILRB2 and blocks interaction of LILRB2 with its all-relevant ligands.
OR502 modulates the immunosuppressive function of TAMs and enhances adaptive anti-tumor responses in M2c/CD8+ T cell coculture assays.
OR502 boosts LPS-induced IFN-γ secretion by peripheral blood mononuclear cells.
The data demonstrate robust anti-tumor activity in humanized mouse models.
Our results support further development of OR502 for cancer immunotherapy.
Accessing Posters
The OncoResponse posters presented at SITC (Free SITC Whitepaper) are accessible on the Publications & Presentations page of the OncoResponse website.

On November 11, 2022 Immunitas Therapeutics ("Immunitas"), a clinical stage precision immunotherapy company committed to discovering and developing novel, differentiated therapeutics for patients with cancer, reported that preclinical data on lead program IMT-009, a fully human monoclonal antibody against a novel immuno-oncology target CD161, today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, held both virtually and in Boston from November 8-12, 2022 (Press release, Immunitas Therapeutics, NOV 11, 2022, View Source [SID1234623852]).

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"The data presented at the 2022 SITC (Free SITC Whitepaper) Annual Meeting demonstrate the potential of IMT-009 as a dual-acting modality that leverages activation of both CD161+ T and NK cells to treat multiple solid and hematological cancers, and further validate our human data-driven approach to developing novel immunotherapies," said Seng-Lai "Thomas" Tan, Ph.D., Chief Scientific Officer of Immunitas Therapeutics. "Our founders discovered a novel population of functional tumor-infiltrating CD161+ T cells, which we believe can be harnessed therapeutically with IMT-009 as a differentiated approach for a better and safer cancer immunotherapy. We look forward to initiating Phase 1/2a clinical evaluation of IMT-009 later this year."

Preclinical data confirm that IMT-009 binds with high affinity and selectivity to CD161, a cell surface inhibitory receptor that is broadly expressed on NK and a subset of memory CD4+ and CD8+ T cells. Upon binding, IMT-009 disrupts CD161 interaction with its ligand, CLEC2D, restoring activation of effector functions of both CD161+ T and NK cells and thus enhancing cytotoxicity towards target tumor cells. GLP toxicity studies in non-human primates demonstrate that once weekly dosing with IMT-009 generates no significant signs of toxicity, indicating a clean safety profile for first-in-human trials. These results support the CLEC2D/CD161 axis as a novel ligand-receptor pathway for immunotherapeutic intervention across a range of solid tumor indications.

The SITC (Free SITC Whitepaper) poster presentation will be available on the Immunitas Therapeutics website on November 11, 2022.

Presentation details are as follows:
Title: Anti-CD161 antibody IMT-009 is a novel immunotherapeutic agent that reinvigorates T and NK cell function and anti-tumor efficacy through blocking interaction of CD161 with its ligand CLEC2D
Abstract Number: 1332
Date/Time: The poster will be presented on November 11, 2022 and made available for in-person attendees from 9:00 am – 8:30 pm ET.

About IMT-009

IMT-009 is a fully human, Fc-attenuated IgG1 monoclonal antibody that binds to CD161 and blocks its interaction with its ligand, CLEC2D. Preclinical data confirm that CD161 blockade with IMT-009 results in enhanced anti-tumor activity. IMT-009 is anticipated to begin enrollment for a Phase 1/2a clinical trial in Q4 2022 for use as a monotherapy and combination treatment for solid tumor and hematological malignancies. The Phase 1 study is designed to evaluate the safety, tolerability, pharmacodynamic biomarkers, and preliminary efficacy of IMT-009 as well as identify the Recommended Phase 2 Dose (RP2D). The trial will then transition into Phase 2 with multiple expansion cohorts to assess the safety and efficacy of IMT-009 alone or in combination with another antineoplastic agent.