On July 24, 2024 Inimmune, a clinical stage biotech company focused on the development of novel immunotherapies, vaccines, and vaccine adjuvants reported the dosing of the first patient in its Phase 1 single ascending dose study of INI-4001 in patients with advanced solid tumors (Press release, Inimmune, JUL 24, 2024, View Source [SID1234645071]).

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This is an open-label, multiple-ascending dose, two-part dose ranging and cohort expansion study of INI-4001 in patients with advanced solid tumors. This first-in-human trial of INI-4001, Inimmune’s proprietary TLR7/8 agonist in a nanoparticle delivery system, will consist of two parts. In Phase 1a, single dose escalation cohorts receiving monotherapy INI-4001 will determine PK, safety, and tolerability. This is followed by Phase 1b where patients who have progressed or have stable disease after 3 cycles of INI-4001 will be allowed to receive concurrent administration of an anti-PD-1 or anti-PD-L1 immunotherapy plus INI-4001.

In pre-clinical studies, INI-4001 was efficacious both as a monotherapy and in combination with anti-PD-1 checkpoint therapy in syngeneic murine tumors (LLC, MC38 and B16F10). Additionally, INI-4001 has been shown to induce production of the cytokine IFNα and activation of antigen presenting cells, leading to downstream T cell activation in vivo. INI-4001 may prove to be an ideal combination agent with checkpoint inhibitors given that a minority of patients currently benefit from checkpoint inhibitor monotherapy.

Inimmune’s CEO, Alan Joslyn, said "We are very excited that INI-4001 clinical trials have commenced, as this marks an important milestone for our company and oncology patients. INI-4001 either as monotherapy or in combination with checkpoint therapy can potentially provide physicians a new therapeutic option in their treatment toolbox."

Inimmune’s trial of INI-4001 is being conducted in Australia and is expected to be complete by the end of 2025. Additional information can be found at clinicaltrials.gov (NCT06302426).

On July 24, 2024 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, reported that it awarded inducement grants on July 22, 2024 to its Executive Vice President and Chief Financial Officer, Edward Dulac, under Intellia’s 2024 Inducement Plan as a material inducement to employment (Press release, Intellia, JUL 24, 2024, View Source [SID1234645040]).

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The inducement grants consisted of non-qualified stock options to purchase 96,219 shares of Intellia’s common stock with an exercise price of $25.33 per share, the closing price of Intellia’s common stock as reported by Nasdaq on July 22, 2024, with 33% of the options underlying the option award vesting on the first anniversary of the grant date and the remainder vesting monthly thereafter until fully vested on the third anniversary of the grant date; time-based restricted stock units ("RSUs") for 66,324 shares of Intellia’s common stock, with one-third of the shares underlying the RSU award vesting on each of the three consecutive anniversaries of the grant date; performance-based RSUs for 33,162 shares of Intellia’s common stock, with vesting criteria linked directly to Intellia’s total stockholder return over a three-year period compared to the companies comprising the Nasdaq Biotechnology Index at the beginning of the performance period; and performance-based RSUs for 30,000 shares (at target) of Intellia’s common stock, with vesting criteria linked directly to certain development milestones over a three-year period.

All equity vesting is subject to Mr. Dulac’s continued service as an employee of, or other service provider to, Intellia through the applicable vesting dates.

All of the above-described awards were granted outside of Intellia’s stockholder-approved equity incentive plans pursuant to Intellia’s 2024 Inducement Plan, which was adopted by the board of directors in June 2024. The awards were approved by a majority of the independent directors of Intellia’s board of directors as a material inducement to Mr. Dulac’s entering into employment with Intellia in accordance with Nasdaq Listing Rule 5635(c)(4).

On July 24, 2024 enGene Holdings Inc. (Nasdaq: ENGN, "enGene" or the "Company"), a clinical-stage genetic medicines company whose non-viral, intravesical lead product candidate, EG-70, is in a pivotal study for BCG-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), reported the grant of an inducement equity award to Ron Cooper, the Company’s newly-appointed Chief Executive Officer (Press release, enGene, JUL 24, 2024, View Source [SID1234645072]).

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The inducement award consists of a non-qualified stock option to purchase 1,250,000 of the Company’s common shares. The option has an exercise price of $8.81 per share, which is equal to the closing price of the Company’s common shares on July 22, 2024, the date of grant. The stock option has a 10-year term and will vest over four years, with 25% of the underlying shares vesting on the one-year anniversary of the grant date and the remainder vesting in equal amounts monthly for three years thereafter, subject to Mr. Cooper’s continued service as an employee of, or other service provider to, the Company through the applicable vesting dates.

The stock option was granted by the Company’s independent Compensation Committee of the Board of Directors as an inducement material to Mr. Cooper entering into employment with the Company in accordance with NASDAQ Listing Rule 5635(c)(4). While the stock option was granted outside of the Company’s Amended and Restated enGene Holdings Inc. 2023 Incentive Equity Plan, it will have terms and conditions consistent with those set forth under the Plan.

On July 24, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable", "Notable Labs" or the "Company"), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Medicine Platform (PMP), reported progress for the Phase 2 volasertib program following receipt of "Clearance to Proceed" from the FDA and agreement on the dosing plan for its Phase 2 clinical trial (Press release, Notable Labs, JUL 24, 2024, View Source [SID1234645041]). With trial start-up activities launched in the first quarter of this year, Notable intends to initiate enrollment in the Phase 2 study for PMP-enabled development of volasertib for relapsed refractory (R/R) acute myeloid leukemia (AML) in the coming months.

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"We are pleased to report positive progress in our clinical development program to evaluate the use of volasertib, in combination with decitabine, for patients with R/R AML. Receiving FDA’s clearance and agreement on a Phase 2 dosing plan positions us to move forward to activate study sites," said Thomas Bock, M.D., Chief Executive Officer of Notable. "AML remains a devastating and life-threatening unmet need, especially for patients whose disease has progressed after first-line treatment, and especially in those who have received venetoclax-based therapies. Advancing the volasertib program through the next Phase 2 implementation steps represents meaningful progress for the Company. We are excited about the potential of volasertib, our predictive platform, and our carefully designed clinical program to enhance patient clinical outcomes and tolerability. We look forward to updating our investors and key stakeholders as we proceed."

Glenn Michelson, M.D., Chief Medical Officer of Notable commented, "Our study design and enrollment strategy for volasertib has been informed by our robust clinical validation trials conducted at Stanford University, the University of Texas MD Anderson Cancer Center and other recognized institutions. In addition, our program incorporates learnings from the agent’s originator, Boehringer Ingelheim, and leverages their extensive post-hoc analysis of the initial Phase 3 AML study. These valuable data guided our decision to in-license volasertib and the overall development strategy. We are enthusiastic to advance a promising new treatment option for patents with R/R AML, building on our platform."

Amer Zeidan, MBBS, Associate Professor of Medicine (Hematology), Chief of Hematologic Malignancies at Yale Cancer Center and study co-chair shared, "As a clinical researcher with experience in acute myeloid leukemia, I am excited about the potential of volasertib, in combination with Notable’s platform and the enhanced trial design, to overcome some of the problems experienced in prior trials of this agent. This study will allow us to understand if volasertib could offer promise to advance care for patients with acute myeloid leukemia."

The Phase 2 study will begin with a dose optimization lead-in and incorporate body-surface area (BSA) dosing, prophylactic antibiotic treatment and best supportive care. The second part of the study is planned to enroll patients with R/R AML who are PMP-predicted responders. The Company is working towards initiating dosing of the first subjects in the Phase 2 trial. Based on our plan, Notable expects to have initial data from the dose optimization lead-in during the fourth quarter of 2024, initiate selective enrollment of PMP-predicted responders after that, and start to report initial efficacy results during H1 2025.

About Volasertib

Volasertib is a PLK-1 inhibitor with demonstrated activity in AML and other tumor types, including solid tumors, with significant unmet medical need. Building on the performance of volasertib on PMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize its PMP to predict volasertib-responsive patients prior to their treatment, with the goal of selectively enrolling and treating those predicted responders, increasing volasertib’s response rates and overall patient outcomes, and fast-tracking volasertib’s remaining clinical development in this patient population. Volasertib was originally developed and manufactured by Boehringer Ingelheim and previously granted Breakthrough Therapy designation by the FDA. Notable in-licensed volasertib and obtained exclusive worldwide development and commercialization rights, except for certain rare pediatric cancers.

On July 24, 2024 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage oncology-focused immunotherapy company developing cancer vaccines and antibody drug conjugate (ADC) therapeutic candidates, reported positive data from a Phase 1 clinical trial of OST-HER2 in patients with HER2-expressing solid tumors in breast cancer and other cancers (Press release, OS Therapies, JUL 24, 2024, View Source [SID1234645073]). Additionally, the Company announced positive preclinical efficacy data for OST-HER2 in multiple models of breast cancer.

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The FDA has granted Rare Pediatric Disease Designation (RPDD), Orphan Drug Designation (ODD), and Fast Track Designation (FTD) for OST-HER2 in Osteosarcoma. OST-HER2, a biologic therapeutic candidate, is a Lm (Listeria monocytogenes) vector-based off-the-shelf immunotherapeutic vaccine designed to prevent metastasis, delay recurrence, and increase overall survival in patients with osteosarcoma and other solid tumors. The proposed OST-HER2 mechanism of action is based on innate and adaptive immune stimulating responses activated by the Lm vector. This treatment generates T cells that can eliminate or slow potential micrometastases that can grow into recurrent osteosarcoma and other solid tumors, including breast cancer. T cell responses home in on HER2 expressed by the tumor and then kill the cell, releasing additional tumor targets. There are currently no approved adjuvant treatments for recurrent osteosarcoma in the United States.

A total of twelve (12) patients with a history of HER2 positive cancer were enrolled in the Phase 1b clinical study, comprised of ten (10) patients with breast cancer, one (1) patient with esophageal cancer and one (1) patient with GE junction cancer. OST-HER2 was determined to be safe and well tolerated in patients with HER2-expressing solid tumors, including at the dose currently being used in the Company’s ongoing Phase 2b clinical trial in recurrent, resected osteosarcoma (AOST-2121, NCT04974008). The Company previously announced positive AOST-2121 interim data and is now in active discussions with the US FDA regarding a Breakthrough Therapy (BTD) designation application submitted for OST-HER2 based on the interim results. The Company is focused on approval for OST-HER2 in osteosarcoma, and thereafter plans to expand development into breast cancer and other HER2 expressing cancers such as esophageal cancer and colorectal cancer.

In addition, the Company announced positive data from multiple preclinical models of breast cancer. The key data for OST-HER2 include:

78% reduction in tumor size (3mm for OST-HER2 treated vs. 14mm for control arm) in FVB/N HER2 transgenic mouse model of breast cancer treatment at day 75
33% prevention of breast cancer in OST-HER2 treated mice vs. 0% prevention of breast cancer in FVB/N HER2 transgenic model of breast cancer prevention at week 50
20% reduction of tumor size for OST-HER2 plus HER2-targeted antibody vs. HER2-targeted antibody alone Tg tumor regression model of breast cancer at day 42
65% reduction cellular concentration of metastatic cells for OST-HER2-treated mice compared with controls in brain metastasis model of primary breast cancer