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Kineta Publishes Preclinical Data Demonstrating the Potential of Anti-VISTA Antibody KVA12123 as an Immunomodulatory Therapy for Cancer

On December 13, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported the peer-reviewed publication in Frontiers in Immunology of preclinical data highlighting the potential of KVA12123 as a new immunotherapy against poorly immunogenic tumors (Press release, Kineta, DEC 13, 2023, View Source;utm_medium=rss&utm_campaign=kineta-publishes-preclinical-data-demonstrating-the-potential-of-anti-vista-antibody-kva12123-as-an-immunomodulatory-therapy-for-cancer [SID1234638530]). The publication titled "A Highly Potent Anti-VISTA Antibody KVA12123 – A New Immune Checkpoint Inhibitor and a Promising Therapy Against Poorly Immunogenic Tumors", reports on the development of KVA12123.

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"This scientific article summarizes the extensive characterization and selection of our clinical candidate KVA12123 that targets VISTA, a strong driver of immune suppression in the tumor microenvironment," said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. "These data demonstrate that our engineered IgG1 anti-VISTA antibody binds to a unique epitope at neutral and acidic pH and has significant potential to address immuno-resistance in cancer patients."

Key results from the publication include:

High affinity binding to VISTA through a unique epitope that is distinct from other clinical-stage anti-VISTA mAbs
High specificity against VISTA with no cross-reactivity against other members of the B7 family
Blockade of VISTA binding to all four of its respective ligands
Ability to reverse T cell suppression by myeloid-derived suppressor cells, one of the main drivers of immune suppression in the tumor microenvironment
Ability to induce T cell and NK-mediated monocyte activation
Strong single-agent antitumor activity in several syngeneic tumor models and enhanced efficacy in combination with anti-PD-1
On-target induction of cytokines/chemokines associated with VISTA blockade
Well tolerated in preclinical toxicology studies without antibody-dependent cellular cytotoxicity or induction of CRS-related cytokines
"We are excited to share the discovery, characterization and preclinical development of KVA12123 in Frontiers in Immunology, a well-known journal in the field," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "The publication highlights the differentiating potency and safety characteristics of KVA12123 that guided its advancement into clinical development. Our Phase 1/2 trial with KVA12123 as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors is on track, demonstrating early promising safety and biomarker results in the clinic."

KVA12123 is currently being evaluated in a Phase 1/2 VISTA-101 open-label clinical trial as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors (NCT05708950). Additional clinical efficacy data in the monotherapy arm and initial combination data with pembrolizumab are anticipated in Q2 2024.

HUTCHMED Announces that it has Completed Enrollment of a Phase II/III Trial of Fruquintinib in Combination with Sintilimab for Advanced Renal Cell Carcinoma in China

On December 13, 2023 HUTCHMED (China) Limited (Nasdaq/AIM:HCM, HKEX:13) ("HUTCHMED") reported that it has completed enrollment of its Phase II/III trial of fruquintinib in combination with sintilimab as second-line treatment for locally advanced or metastatic renal cell carcinoma ("RCC") in China (Press release, Hutchison China MediTech, DEC 13, 2023, View Source [SID1234638529]).

The study is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of fruquintinib in combination with sintilimab versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC. The primary endpoint is progression free survival ("PFS") per RECIST 1.1 as assessed by blinded independent central review (BICR). The secondary endpoints include objective response rate ("ORR"), disease control rate ("DCR"), duration of response ("DoR"), time to response (TTR), overall survival ("OS"), safety, and quality of life. A total of 234 patients have been enrolled in the study. The leading principal investigators are Dr Dingwei Ye of Fudan University Shanghai Cancer Center and Dr Zhisong He of Peking University First Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT05522231.

The first patient in China received the first dose on October 27, 2022 and HUTCHMED expects to announce topline results from the study around year end 2024. If favorable, the results would enable a New Drug Application submission to China’s National Medical Products Administration ("NMPA").

About Kidney Cancer and RCC

It is estimated that approximately 430,000 new patients were diagnosed with kidney cancer worldwide in 2020.1 In China, an estimated 74,000 new patients were diagnosed with kidney cancer in 2020.2 Approximately 90% of kidney tumors are RCC.

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

About Fruquintinib and Second-line treatment of RCC

Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors ("VEGFR") -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. Fruquintinib has demonstrated a manageable safety profile and is being investigated in combination with other anti-cancer therapies including the approved PD-1 inhibitor, sintilimab.

The U.S. Food and Drug Administration ("FDA") has approved five immune-oncology combination therapies for first-line treatment of advanced RCC, however, no immune-oncology combination therapies have been approved in China, indicating an unmet medical need in these settings.

As presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper), a proof of concept study of fruquintinib plus sintilimab demonstrated promising efficacy and tolerable safety profile in this setting. At the data cutoff date of November 30, 2022, all 20 enrolled previously treated patients were efficacy evaluable, and median follow-up duration was 23.3 months. The confirmed ORR was 60.0% and DCR was 85.0%. Median DoR was 13.9 months and mPFS was 15.9 months. OS was not reached.

Entry into a Material Definitive Agreement

On December 13, 2023, Genprex, Inc. (the "Company") reported to have entered into an At The Market Offering Agreement (the "Agreement") with H.C. Wainwright & Co., LLC, serving as agent (the "Agent") with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.001 per share (the "Common Stock"), having an aggregate offering price of up to $25.0 million (the "Shares") through the Agent (the "Offering"). Any Shares offered and sold in the Offering will be issued pursuant to the Company’s shelf Registration Statement on Form S-3 (File No. 333-271386) filed with the Securities and Exchange Commission (the "SEC") on April 21, 2023, which was declared effective on June 9, 2023, the related prospectus contained therein, and the prospectus supplement relating to the Offering to be filed with the SEC on December 13, 2023 and any applicable additional prospectus supplements related to the Offering that form a part of the Registration Statement (Filing, 8-K, Genprex, DEC 13, 2023, View Source [SID1234638528]).

The Agent may sell the Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, including, without limitation, sales made through The Nasdaq Capital Market ("Nasdaq") or on any other existing trading market for the Common Stock. The Agent will use commercially reasonable efforts to sell the Shares from time to time consistent with its normal sales practices and applicable federal rules, regulations and Nasdaq rules, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay the Agent a commission equal to three percent (3%) of the gross sales proceeds of any Shares sold through the Agent under the Agreement, and also has provided the Agent with customary indemnification and contribution rights.

The Agent is not required to sell any specific number or dollar amount of securities, but will use commercially reasonable efforts to sell, on behalf of the Company, all of the shares of common stock requested to be sold by the Company, consistent with its normal trading and sales practices, on mutually agreed terms between the Agent and the Company. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. A copy of the opinion of Lowenstein Sandler LLP relating to the legality of the issuance and sale of the shares in the Offering is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

Fate Therapeutics Reports New Employee Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

On December 13, 2023 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported that the Company granted a non-qualified stock option to one newly-hired employee to purchase a total of 350,000 shares of the Company’s common stock at an exercise price per share of $2.28, which was the closing price per share of the Company’s common stock as reported by NASDAQ on the grant effective date of December 11, 2023 (Press release, Fate Therapeutics, DEC 13, 2023, View Source [SID1234638527]). The option was approved by the Compensation Committee of the Company’s Board of Directors and granted under the Company’s Amended and Restated Inducement Equity Plan as an inducement material to the new employee entering into employment with the Company in accordance with Nasdaq Listing Rule 5635(c)(4). The option vests over four years, with 25% vesting on the one-year anniversary of the grant date and the remaining 75% percent vesting in approximately equal monthly installments over the following thirty-six months, subject to the employee being continuously employed by the Company through each vesting date.

Black Diamond Therapeutics Announces Topline Results from Phase 1 Dose Escalation Trial of BDTX-1535 in Patients with Recurrent GBM

On December 13, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported topline results from the dose escalation portion of the Phase 1 clinical trial of BDTX-1535 in patients with recurrent glioblastoma (GBM) who expressed epidermal growth factor receptor (EGFR) alterations at the time of their initial diagnosis (Press release, Black Diamond Therapeutics, DEC 13, 2023, View Source [SID1234638526]). BDTX-1535, a fourth-generation, brain-penetrant, covalent EGFR inhibitor, is under investigation in a Phase 1 clinical trial for the treatment of patients with non-small cell lung cancer (NSCLC) or GBM.

"These initial results in patients with recurrent GBM are encouraging, as there are no approved therapies available for those who progress following initial treatment, and there is strong rationale for a brain penetrant, covalent EGFR inhibitor such as BDTX-1535 to have a meaningful impact in earlier lines of therapy," said Patrick Wen, M.D., Director of The Center for Neuro-Oncology at Dana-Farber Cancer Institute.

Clinical data as of November 2023 reflect 27 patients with recurrent GBM who received a range of doses spanning 15mg to 400mg once daily (QD) in the dose escalation cohort. Combined pharmacokinetic (PK) and safety data from these 27 patients with GBM and 27 patients with NSCLC were previously presented on October 14, 2023 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). No new safety signals were observed; adverse events were consistent with the EGFR tyrosine kinase inhibitor (TKIs) class of drugs, including primarily Grade 1 and 2 diarrhea and rash. Patients with NSCLC dosed at 100mg QD or greater demonstrated confirmed partial responses in lung lesions and CNS metastases.

Key enrollment and inclusion factors

Of the 27 patients with recurrent GBM, 22 were started at or escalated to a dose of 100mg QD or greater and reached at least one post baseline tumor assessment.
Patients were heavily pretreated, with a median of 2 prior lines of therapy (range 1-4). All patients except one had received prior temozolomide. Other prior treatments included chemotherapy, bevacizumab, checkpoint inhibitors or investigational agents.
Patients were required to have EGFR alterations at the time of diagnosis, but EGFR status was not known at time of treatment with BDTX-1535 as biopsies are not commonly performed for recurrent disease.
Key results

Of the 22 patients evaluable for efficacy, 3 patients were on therapy longer than 10 months, 1 patient longer than 6 months, and 5 patients longer than 4 months. Historical progression-free survival (PFS) in this population is in the range of 2-4 months.
The patient on therapy the longest remains on BDTX-1535 at 100mg QD for over 15 months with prolonged disease stabilization. This patient had previously progressed after 3 months of temozolomide treatment.
Of the 19 patients with measurable disease by Response Assessment in Neuro-Oncology (RANO) criteria, 1 patient achieved a confirmed partial response (PR) and 8 patients experienced stable disease (SD). The patient with the PR stayed on treatment for longer than 4 months at 200 mg QD.
Black Diamond plans to submit results from the dose escalation GBM cohort for presentation at a medical meeting in the second quarter of 2024. Enrollment is ongoing in a "window of opportunity" clinical trial of BDTX-1535 in second-line patients with high-grade glioma. The trial (NCT06072586) is sponsored by the Ivy Brain Tumor Center in Phoenix, Arizona and is enrolling patients prior to a planned resection in order to assess PK and pharmacodynamics (PD) in brain tissue. Patients achieving adequate drug levels in the gadolinium non-enhancing regions of the tumor will continue with treatment following surgery. The trial will enroll up to 22 patients, and clinical data is expected in the second quarter of 2024.

"We believe the ‘window of opportunity’ trial of BDTX-1535 will provide valuable information on both drug levels in the brain and clinical activity in second-line patients, and will inform potential next steps in our development program," said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. "More than half of all newly diagnosed GBM patients express an altered form of EGFR, and preclinical data demonstrate BDTX-1535 potently inhibits this spectrum of alterations. Therefore, BDTX-1535 may be optimally suited to benefit first-line patients."

About BDTX-1535

BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC), including families of non-classical driver mutations (e.g., L747P, L718Q), acquired resistance C797S mutation, and complex mutations. BDTX-1535 is a fourth generation TKI that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. Dose escalation of BDTX-1535 in patients with GBM is complete and dose expansion is currently ongoing in patients with NSCLC (NCT05256290).