InnoCare Announces Clearance of Clinical Trial of BCL2 Inhibitor ICP-248 by U.S. FDA

On January 16, 2024 InnoCare Pharma (HKEX: 09969; SSE: 688428), a commercial-stage biotech company, reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Company’s B-cell lymphoma-2 (BCL2) inhibitor, ICP-248 (Press release, InnoCare Pharma, JAN 16, 2024, View Source [SID1234639283]). This is InnoCare’s fifth innovative drug to enter the clinical stage in the U.S.

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This is a Phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of ICP-248 in hematologic malignancy patients.

ICP-248 is a novel, orally bioavailable BCL2-selective inhibitor, which aims to treat hematologic malignancies as a monotherapy or in combination with other therapies. The Phase I dose escalation trial of ICP-248 is ongoing in China, and the preliminary results demonstrated good efficacy and safety profiles.

BCL2 is an important regulatory protein of the apoptosis pathway, and its abnormal expression is related to the development of various hematologic malignancies. ICP-248 exhibits its anti-tumor effects by selectively inhibiting BCL2 and restoring the mechanism of programmed cell death.

Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare said, "ICP-248 would become an important asset for the Company’s globalization after orelabrutinib. The current study results will support ICP-248 to treat hematologic malignancies as a monotherapy or in combination with other therapies. Meanwhile, InnoCare is dedicated to building a leading franchise in hemato-oncology, and we have developed multiple drugs that cover a variety of important hemato-oncology targets such as BTK, CD19, CD20xCD3, BCL2 and E-3 ligase to address unmet medical needs."

Adagene Presents Interim Results Reinforcing Best-in-Class Profile of Masked anti-CTLA-4 SAFEbody® ADG126 (muzastotug) in Combination with Pembrolizumab in Metastatic Microsatellite-stable (MSS) Colorectal Cancer (CRC)

On January 16, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported data from its presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Gastrointestinal (GI) Cancers Symposium, taking place January 18-20 in San Francisco (Press release, Adagene, JAN 16, 2024, View Source [SID1234639248]).

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"The expanded therapeutic index for the masked ADG126 allows us to dose with a higher and more frequent effective dose of anti-CTLA-4 therapy than today’s options," said Daneng Li, MD and Associate Professor Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center. "These promising data support further evaluation of this potential best-in-class anti-CTLA-4 antibody, ADG126, in combination with pembrolizumab for MSS CRC patients, including battling new liver lesions in those patients initially without detectable liver metastasis. We also see a tremendous opportunity to help patients in other tumor types where there is a significant need for safe and potent anti-CTLA-4 therapy."

Key highlights from the poster (November 30, 2023 data cutoff) include:

· Results from dose escalation and dose expansion cohorts of ADG126 in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) (200 mg/Q3W) demonstrated a best-in-class safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46):
o Limited dose-dependent toxicities were observed.
o Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46).
· In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than 55 weeks (over 14 cycles) of treatment.
· In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W:
o Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.
o An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate 100% (2 PRs and 7 SD).
o Observation of these clinical activities triggered further expansion into Stage 2 of the Simon’s 2-stage design for this dose level, which is currently ongoing with data anticipated throughout 2024.
· In a preliminary PFS analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.

Commenting on the results, Heinz Josef-Lenz, MD, FACP, Associate Director for Clinical Research and Co-leader of the Translational Science Program at the USC Norris Comprehensive Cancer Center (NCCC) said, "I believe that CTLA-4 is an essential part of an effective immunotherapy for MSS CRC, yet physicians have been limited by the safety challenges from first generation options. The clinical profile of ADG126 in combination with pembrolizumab presents a great opportunity for MSS CRC patients that otherwise have limited immunotherapy options available."

ASCO-GI Poster Presentation Details

Title: Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody) in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic microsatellite-stable (MSS) colorectal cancer (CRC)

· Date: Saturday, January 20
· Time: 6:30 a.m. – 7:55 a.m. Pacific Time
· Onsite Location: Moscone West
· Abstract Number: 127
· Poster Board: H12

Consistent with the ASCO (Free ASCO Whitepaper)-GI embargo policy, the data are being released today in conjunction with the abstract publication.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Vaxart Announces $10.0 Million Registered Direct Offering with RA Capital Management

On January 16, 2024 Vaxart, Inc. (Nasdaq: VXRT) reported that it has entered into a common stock purchase agreement with RA Capital Management for the sale of 15,384,615 shares of its common stock in a registered direct offering at an offering price of $0.65 per share (Filing, 8-K, Vaxart, JAN 16, 2024, View Source [SID1234639264]).

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Gross proceeds are approximately $10.0 million, before deducting expenses payable by Vaxart. Vaxart intends to use the net proceeds from the offering primarily for general corporate purposes, including working capital, operating expenses and capital expenditures.

"We appreciate the financial backing by RA Capital as we continue to progress our oral pill vaccine platform," said Dr. Michael J. Finney, Vaxart’s Interim Chief Executive Officer. "We believe the clinical proof of data we have generated to date has validated our platform, which carries transformative potential to change how people get vaccinated globally. With this financing, we can continue to advance our programs, with the goal of bringing to market oral pill vaccine(s) that carries significant public health benefits."

The closing of the registered direct offering is expected to occur on or about January 18, 2024, subject to the satisfaction of customary closing conditions.

The shares of common stock are being offered by Vaxart pursuant to a shelf registration statement on Form S-3. A final prospectus supplement and accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and is available on the SEC’s website at www.sec.gov.

Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained when available, on the SEC’s website at View Source or by contacting Vaxart Investor Relations, 170 Harbor Way, Suite 300, South San Francisco, CA 94080, by email: [email protected] or by telephone: (650) 550-3500.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities described herein, 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 the registration or qualification under the securities laws of any such state or jurisdiction.

Data from a Phase 1b Study of Quemliclustat-Based Regimens Showed Promising Overall Survival in Treatment-Naïve Metastatic Pancreatic Cancer

On January 16, 2024 Arcus Biosciences, Inc. (NYSE:RCUS) reported promising overall survival data from ARC-8, a Phase 1b study that is being co-developed with Gilead Sciences. ARC-8 is the study of quemliclustat, an investigational small molecule CD73 inhibitor, plus chemotherapy with or without zimberelimab, an investigational anti-PD-1 antibody, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) (Press release, Arcus Biosciences, JAN 16, 2024, View Source [SID1234639284]). The results will be presented during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI).

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"A quemliclustat-based regimen appears to meaningfully prolong survival compared to what we typically observe in patients with mPDAC who receive chemotherapy alone, the standard of care for more than 30 years," said Zev A. Wainberg, MD, MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-8 trial. "CD73 is highly expressed on pancreatic cancer cells, and I am encouraged to see early evidence that inhibiting CD73 with a small molecule has the potential to improve outcomes for people with mPDAC, without an observed clinically meaningful increase in toxicity, when combined with standard of care chemotherapy relative to historical data for chemotherapy alone."

The results to be presented include data from all patients (n=122) with treatment-naïve (first-line) mPDAC who received 100mg of quemliclustat plus chemotherapy with or without zimberelimab in the dose-escalation, dose-expansion and randomization cohorts of ARC-8. The data cutoff was June 19, 2023. Median overall survival (mOS) data for both quemliclustat-based regimens were numerically greater than historical benchmark data for chemotherapy alone, which has shown a mOS of approximately nine months.

An analysis was performed by the Medidata AI team, part of Medidata, a Dassault Systèmes company, whereby they constructed a Synthetic Control Arm of patients who were treated with gemcitabine/nab-paclitaxel in Phase 2 and 3 clinical studies in the first-line metastatic pancreatic cancer setting, on a post-hoc basis. Patients from these studies were matched 1:1 to the pool of 122 patients treated with the 100 mg quemliclustat-based regimens in ARC-8, based on demographics and key baseline characteristics such as ECOG performance status, liver metastasis, and history of prior surgery. The matched SCA was constructed based on a pre-specified analysis plan before OS data were unblinded and analyzed by the Medidata AI team. The analysis showed that the patients in ARC-8 lived longer than patients from the matched control arm. Specifically, these results showed that patients in ARC-8 experienced a:

37% reduction in the risk of death, HR=0.63 (CI: 0.47 – 0.85, p=0.0030) and a
5.9-month increase in mOS (15.7 vs 9.8 months) relative to the matched control arm.
The efficacy data for the pooled dose-escalation, dose-expansion and randomized arms, as well as the data from the SCA, are summarized below:

A2: Q+G/nP*
(n=29)

A1: QZ+G/nP**
(n=61)

Pooled Q100
QZ+G/nP***
(n=93)

All Pooled Q100
Q±Z+G/nP
(n=122)****

Post-hoc
Synthetic
Control Arm
(n=122)*****

Median OS, months (95% CI)

19.4 (12.1, 23.0)

14.6 (10.6, 21.5)

13.9 (11.1, 18.7)

15.7 (12.4, 20.9)

9.8 (7.8, 11.4)

Hazard Ratio

(95% CI)

HR=0.63 (0.47 – 0.85)

p=0.0030)

12-month OS

72.3%

60.9%

59.6%

62.7%

41.1%

Median PFS, months (95% CI)

8.8 (6.4, 12.6)

4.9 (3.7, 6.0)

5.4 (4.9, 7.3)

6.3 (5.4, 7.7)

5.5 (4.4, 6.6)

Hazard Ratio

(95% CI)

HR=0.78 (0.58‑1.05)

p=0.1102

ORR, % (95% CI)

41 (24, 61)

34 (23, 48)

38 (28, 48)

39 (29.9, 47.8)

41 (32.2, 50.3)

Q, Quemliclustat; Z, Zimberelimab; G/nP, gemcitabine / nab‑paclitaxel; CI, confidence interval
*Cohort A2 – patients randomized to Q+G/nP in the dose-expansion phase.
**Cohort A1 – patients randomized to QZ+G/nP in the dose-expansion phase.
***Pooled Q100 QZ+G/nP – treatment-naïve patients receiving 100 mg of quemliclustat plus zimberelimab and G/nP across dose- escalation, expansion and randomization phases.
****All Pooled – treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose- escalation, dose-expansion and randomization phases.
*****Synthetic Control Arm (Historical Control) – Historical clinical trial data from patients treated with G/nP, balanced to the baseline characteristics of ARC-8 participants. The Synthetic Control Arm data were compared to the All Pooled group.

No new safety signals were observed in the study. The most common adverse events (Grade 3 or higher) were neutropenia (37.9%, 34.4% and 38.7%) and anemia (27.6%, 26.2% and 23.7%), respectively, for cohorts A2, A1 and Pooled Q100 QZ+G/nP. Five deaths were reported, and none were considered by the study investigators to be related to quemliclustat or zimberelimab.

Quemliclustat and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of pancreatic cancer have not been established.

About Quemliclustat

Quemliclustat is an investigational, potent and selective small molecule CD73 inhibitor. CD73 is the primary enzymatic producer of immunosuppressive adenosine in the tumor microenvironment, and high CD73 expression is associated with significantly poorer prognosis in several tumor types. Quemliclustat has been shown to block the production of adenosine. Once the immunosuppressive effects of adenosine are removed, activation of antitumor immune cells may be restored, resulting in cancer cell death.

Arcus and Gilead are currently evaluating quemliclustat in combination with other molecules within the collaboration portfolio with chemotherapy, including Phase 2 studies in lung and upper gastrointestinal cancers.

About the ARC-8 Trial

The ARC-8 trial is a Phase 1b, open-label, dose-escalation and dose-expansion platform study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of combinations of the small molecule CD73 inhibitor quemliclustat, anti-PD-1 antibody zimberelimab and chemotherapy (gemcitabine / nab‑paclitaxel, or G/nP) in participants with advanced pancreatic cancer.

After the dose-escalation phase, quemliclustat 100 mg was selected as the dose for expansion. Patients were treated with quemliclustat 100 mg every two weeks plus standard doses of chemotherapy and zimberelimab (240 mg IV every two weeks) in Cohort A (treatment-naïve mPDAC) of the dose-expansion phase and then randomized 2:1 to receive quemliclustat plus zimberelimab and chemotherapy (Cohort A1) or quemliclustat plus chemotherapy (Cohort A2). Pooled analyses were conducted to reflect: 1) all treatment-naïve patients who received quemliclustat 100 mg plus zimberelimab and chemotherapy from dose-escalation and dose-expansion phases and 2) all treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose-expansion and escalation phases. Endpoints included safety, overall response rate, median overall survival and progression‑free survival. More information about ARC-8 is available at: View Source

Additionally, an analysis comparing the All Pooled cohort to a Synthetic Control Arm (SCA) was conducted to address the differences in patient characteristics in the study cohorts, particularly in relation to decreased presence of liver metastases at baseline in cohort A2. The SCA consisted of historical clinical trial data from patients treated with G/nP, with baseline characteristics matched to those of ARC-8 participants.

About Pancreatic Cancer

Pancreatic cancer occurs in the pancreas, an organ located behind the stomach that helps with digestion and controlling blood sugar. Pancreatic cancer is one of the most aggressive cancers, with a dismal prognosis. Approximately 50% of patients with PDAC are diagnosed in the metastatic setting, which is associated with a 5-year survival rate of only 3%. Over 80% of pancreatic cancers are diagnosed at a late stage. The majority (over 90%) of pancreatic cancers are adenocarcinomas, a type of cancer that forms in tissues that line certain internal organs and release fluids like those that help with digestion. There have been limited advancements for treating pancreatic cancer, and chemotherapy has been the standard of care for more than 30 years.

Cellectar Biosciences Broadens Pipeline with Targeted Alpha Therapy (TAT) for Solid Tumors and Releases Promising Preclinical Data

On January 16, 2024 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported promising preclinical data for its proprietary novel alpha-emitting phospholipid radiotherapeutic conjugate, CLR 121225 (225Ac-CLR 121225) an actinium-labeled phospholipid ether (PLE), in pancreatic cancer models (Press release, Cellectar Biosciences, JAN 16, 2024, View Source [SID1234643477]). The development of this compound will expand the company’s clinical pipeline of PLE cancer targeting compounds to include targeted alpha therapies (TATs), complementing its beta-emitting phospholipid radiotherapeutic conjugate, iopofosine I 131, which achieved its primary endpoint in the CLOVER WaM pivotal study in highly refractory Waldenstrom’s macroglobulinemia patients.

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Cellectar’s PLE platform may provide unique advantages which overcome the issues experienced by existing TAT delivery platforms. While current TAT platforms, such as antibodies and peptides, possess the potential to be effective for treating cancers with low tumor volume, they are challenged to treat higher volume or bulky tumors due to insufficient penetration and the need for high quantities of the target epitope. Cellectar’s PLE’s possess biochemical properties that enable penetration of the TAT payload deep into the tumor mass and the abundance of lipid rafts on tumor cells provides near universal delivery and enhanced outcomes.

"The advancement of our TAT program is part of our overall strategy to develop a comprehensive portfolio of first- and best-in-class radiotherapeutics designed to treat both blood cancers and solid tumors that now includes both alpha and beta-emitting radiotherapeutics," commented James Caruso, president and CEO of Cellectar. "Our promising preclinical data with actinium-225 highlights the potential utility of our PLE platform to provide targeted delivery to nearly any isotope resulting in compounds with excellent activity and tolerability. Our novel TAT compounds, including actinium-225, lead-212 and others, have demonstrated this potential in pancreatic cancer, triple-negative breast cancer and other types of tumor models which allows us to deliver the optimal radioisotope based on tumor biology to maximize outcomes. These data provide further evidence supporting the continued development of CLR 121225, which is expected to enter a Phase 1 first-in-human study later this year or early next year."

In preclinical studies, CLR 121225 demonstrated potent anti-tumor activity in refractory pancreatic cancer mouse xenograft models. A single administration at each dose level (100nCi, 250nCi and 500nCi) resulted in tumor volume reduction in a dose dependent manner with the highest dose providing near complete eradication of the tumor. Additionally, it was shown that CLR 121225 demonstrated excellent biodistribution; approximately 15 – 20% of the infused drug accumulated in the tumor within four hours and continued to accumulate over 72 – 96 hours. The mice had no end organ toxicities demonstrating good tolerability. The data are consistent with experiments using other alpha emitters conjugated to the company’s proprietary PLE targeted delivery platform.