On April 15, 2024 Imugene Limited (ASX: IMU), a clinical stage immuno-oncology company, reported that enrolment has opened for its expansion study in bile tract cancer (cholangiocarcinoma) patients, having completed the fifth, high dose cohort in the intratumoural (IT) arm of the monotherapy dose escalation study evaluating its cancer-killing virus CF33-hNIS (VAXINIA) (Press release, Imugene, APR 15, 2024, https://mcusercontent.com/e38c43331936a9627acb6427c/files/d90ab1d4-f16c-5d92-40f9-240afd491d30/Bile_Tract_Cancer_Study_Opens_after_MAST_High_Dose_Clearance.pdf [SID1234642044]).

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Imugene Managing Director & CEO Leslie Chong said: "As a team we’re particularly eager to begin the cholangiocarcinoma expansion study, given the meaningful difference we’ve seen VAXINIA make for patients with gastrointestinal cancers, including one patient with cholangiocarcinoma who achieved a complete response and another who achieved stable disease. It’s timely for enrolment to open as we present our VAXINIA technology to the 2024 Cholangiocarcinoma Foundation Annual Conference later this week."

The expansion of the MAST (Metastatic Advanced Solid Tumours) Phase 1 trial is planned for 10 patients with bile tract cancers, after early positive responses were observed in gastrointestinal cancers, particularly in cholangiocarcinoma.

Cholangiocarcinoma is a rare disease in which malignant cancer cells form in the bile ducts. It is difficult to treat and generally responds poorly to immunotherapy drugs.

One patient with cholangiocarcinoma who had failed three prior lines of therapy received a mid-dose of IT-administered monotherapy VAXINIA achieved a complete response, meaning the disappearance of all signs of cancer in response to treatment, with no known recurrence in more than 430 days. A second patient with cholangiocarcinoma, who has also progressed on prior drug therapies, achieved stable disease for more than four months upon receiving IV-administered VAXINIA.

In November 2023, the FDA granted the VAXINIA MAST clinical program Fast Track Designation for the treatment of bile duct cancer (cholangiocarcinoma), which allows Imugene closer cooperation with the FDA to expedite the program and potential approval process. This designation followed the promising data detailing Phase 1 efficacy and tolerability.

On Friday 12 April 2024, the Cohort Review Committee cleared the fifth cohort in the IT arm of the monotherapy dose escalation portion of the MAST trial, with no safety signals seen to date. In addition to the patients dosed in the monotherapy dose escalation portion of the trial, enrolment is ongoing for the VAXINIA and pembrolizumab combination portion of the trial, with 16 patients dosed to date.

The multicenter, Phase 1, MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. With no safety signals identified to date, the trial has since progressed through the monotherapy dose escalation cohorts as well as the combination study, whereby VAXINIA is administered with well-known checkpoint inhibitor pembrolizumab. CF33 oncolytic virus, developed by City of Hope, has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models.

On April 12, 2024 Illumina, Inc. (NASDAQ: ILMN), a global leader in DNA sequencing and array-based technologies, reported it has received approval of its divestment plan for GRAIL from the European Commission (EC) (Press release, Illumina, APR 12, 2024, View Source [SID1234642040]).

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While this does not mean the method of divestment has been finalized, the company is pleased to reach an agreement with the EC on specific divestment options as it represents an important milestone in the process. Illumina continues to explore divesting GRAIL through either a trade sale or a capital markets transaction, each of which are contemplated by the plan approved today. In the event of a capital markets transaction, Illumina must capitalize GRAIL with two-and-a-half years of funding, which is estimated at approximately $1 billion based on GRAIL’s long-range plan.

Illumina looks forward to working with the EC on approval of final terms consistent with the divestment plan. As previously stated, Illumina has a goal of finalizing those terms by the end of the second quarter of 2024.

On April 12, 2024 TransThera Sciences, a clinical-stage biopharmaceutical company focused on inventing differentiated drugs for global patients, reported the poster presentation at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) to discuss the latest breaking research of tinengotinib for patients with advanced solid tumors harboring actionable FGFR1-3 alterations (Press release, TransThera Biosciences, APR 12, 2024, View Source [SID1234642039]).

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Monotherapy for patients with advanced solid tumors harboring actionable FGFR1-3 mutations:

Fibroblast growth factor receptor (FGFR) alterations occur across various malignancies and are potent oncogenic drivers in multiple tumor types. FGFR inhibitors have demonstrated efficacy in several cancers with FGFR alterations. However, no effective therapies are available worldwide for patients with advanced solid tumors harboring actionable FGFR1-3 mutations currently.

Tinengotinib is a unique multi-kinase inhibitor that has very distinct binding mode to FGFR 1-3 proteins, rendering it highly potent to a series of FGFR mutations, including gatekeeper mutations, molecular brake mutations, cystine binding site mutations, and others. This feature has made it highly differentiated from existing FGFR inhibitors, indicating its potential to target cancer patients bearing a broad range of FGFR mutations.

The retrospective analysis of the pooled results from four clinical studies of tinengotinib in advanced solid tumors harboring actionable FGFR1-3 mutations showed efficacy in multiple tumor types, including cholangiocarcinoma, breast, prostate, urothelium, colon and head and neck cancer. Our data demonstrate 33.3% BOR and 88.2% DCR, 6.90 months mPFS. The promising results validated the novel mechanism of tinengotinib and clinical applications for potentially FGFR 1-3 altered patients with solid tumors.

About tinengotinib

Tinengotinib is an innovative, global phase III stage spectrum-selective kinase inhibitor that exerts antitumor effects by targeting tumor cells proliferation, angiogenesis and immune-oncology pathways by inhibiting the cytokine signaling and angiogenesis (FGFRs and VEGFRs), mitotic kinases Aurora A/B and Janus kinases (JAK). Ongoing clinical trials in the US and China have revealed the potential of tinengotinib to be efficacious in various solid tumors. It was granted the Orphan Drug Designation and Fast Track Designation by the FDA for the treatment of CCA, the Breakthrough Therapy Designation (BTD) by NMPA in China, the Orphan Drug Designation(ODD) for the treatment of biliary tract cancer by EMA.

On April 12, 2024 Agenus Inc. (NASDAQ: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, reported updated results from its Phase 1 clinical trial of BOT/BAL combination therapy in patients with metastatic CRC that is not microsatellite instability-high (MSS) or deficient mismatch repair (dMMR) (Press release, Agenus, APR 12, 2024, View Source [SID1234642038]). These findings build upon the compelling clinical activity demonstrated by BOT/BAL across nine different cancer types in Agenus’ broad clinical development program.

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In the Phase 1 trial of 77 patients with refractory MSS-CRC without active liver metastases, a 23% overall response rate (ORR) was observed after a median follow up of 13.6 months at the data cutoff of March 1, 2024. The median duration of response in 18 responders was not yet reached. The estimated 12-month and 18-month OS rates were 71% and 62%, respectively. The median OS was 21.2 months.

The Phase 2 trial has completed enrollment and the company plans to discuss the encouraging interim results with the U.S. Food and Drug Administration (FDA).

"These results underscore the potential of BOT/BAL in metastatic CRC, the second leading cause of cancer mortality in the U.S.," said Steven O’Day, M.D., Chief Medical Officer at Agenus. "We continue to work expeditiously to bring this promising combination to patients in need."

Pending planned meetings with the FDA, Agenus plans to submit a Biologics License Application (BLA) for BOT/BAL in refractory MSS CRC later this year and plans to present detailed Phase 2 efficacy results, including response durability and updated Phase 1 survival data, at a major medical conference in the second half of 2024. This growing body of clinical evidence underscores the significant potential of BOT/BAL to transform the treatment landscape for difficult-to-treat solid tumors.

On April 12, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable" or the "Company"), a clinical-stage precision oncology company developing new cancer therapies identified by its Predictive Precision Medicine Platform (PPMP), reported financial results for the year ended December 31, 2023 and provided a business update (Press release, Notable Labs, APR 12, 2024, View Source [SID1234642037]).

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"The last year has been a time of great accomplishment for Notable. We built a strong clinical validation dataset, starting with a poster presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2023); became a publicly listed company, following the closing of a reverse merger in October 2023; and reported successful PPMP clinical data from the Phase 2 fosciclopirox study that showcased the ability of our platform to accurately predict patient outcomes for specific therapeutics," said Thomas Bock, M.D., Chief Executive Officer of Notable. "The performance of our platform in accurately predicting the outcome of the fosciclopirox study has enabled us to enhance the clinical trial plan for our lead product candidate, volasertib, in development for patients with relapsed/refractory acute myeloid leukemia (r/r AML). In our upcoming Phase 2 trial, we will be utilizing the platform to enrich the study’s enrollment with patients predicted to respond to volasertib, which we believe will result in more rapid enrollment, shorter time to efficacy data and, ultimately, increased probability of success."

Dr. Bock commented further, "Looking ahead, we are on track to significantly advance the clinical program for volasertib in 2024 and further validate the potential for PPMP as a precision medicine tool. We are pleased that an abstract related to this program was presented this week at the AACR (Free AACR Whitepaper) 2024 and look forward to providing additional data in the coming months."

Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, added, "We are enthusiastic to initiate the Phase 2 volasertib/PPMP trial in the coming months. Our study will incorporate important learnings from prior studies conducted by volasertib’s originator, Boehringer Ingelheim, which suggest that standardizing best supportive care and introducing body surface area-based dosing are likely to enhance patient responses and tolerability. We plan to include and evaluate these refinements in a small
all-comers dose optimization lead-in, prior to enrolling PPMP-predicted responders. The open label design of our Phase 2 trial will enable us to provide ongoing updates and initiate a subsequent Phase 3 trial at the earliest possibility."

Recent and Upcoming Milestones:

● Presentation of two posters at AACR (Free AACR Whitepaper)2024: April 8 and 9, 2024

● Volasertib: Advance the Phase 2 program, starting with the dose optimization prelude

Year End December 31, 2023 Financial Results

Total cash and cash equivalents (Cash) were $11.8 million as of December 31, 2023. As of April 1, 2024, Notable has cash and cash equivalents of $8.2 million. Based on its current cash position and the Company’s planned expense run rate, the Company believes that its current cash balance is sufficient to support its planned expenses, obligations and capital expenditure requirements into Q4 2024.

Total net revenue includes revenue from diagnostic services performed on a limited basis as an outsourced provider. Total net revenue for the year ended December 31, 2023 was $0.3 million.

Total cost of services relate to the costs of processing diagnostic tests of laboratory samples. Total cost of services for the year ended December 31, 2023 was $0.2 million.

Research and development expenses for the year ended December 31, 2023 were $4.7 million, compared to $7.8 million in 2022, reflecting lower engineering costs necessary to support the PPMP platform, as well as lower laboratory costs for fosciclopirox and volasertib.

General and administrative expenses for the full year 2023 were $10.1 million compared to 5.2 million in 2022, mainly reflecting increased third-party costs related to the merger completed in October 2023, as well as higher costs associated with being a public company, including Directors and Officers Insurance (D&O) and stock-based compensation.

Other Income (Expense), Net for the full year 2023 increased to $3.4 million of other income, net, from an expense of $1.5 million in 2022. The increase was primarily due to the loss on the conversion of the Series D SAFEs, the increase in the derivative fair value of the Series C SAFE and redeemable convertible preferred stock warrant liability.

Net loss for 2023 decreased to $(11.3) million, or a loss of $(3.41) per share on a basic and diluted basis, for the year ended December 31, 2023, versus a net loss of $(14.4) million, or a loss of $(21.97) per share on a basic and diluted basis, for the year ended December 31, 2022.

Outstanding shares as of April 1, 2024 were approximately 9.0 million.

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 PPMP, an important and proprietary step during Notable’s targeted in-licensing strategy and decision making, Notable will utilize PPMP 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.