On December 10, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported positive initial data from CRDF-004, a randomized, Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC) (Press release, Cardiff Oncology, DEC 10, 2024, View Source [SID1234648975]). Efficacy and safety data are for all evaluable patients as of a November 26, 2024 data cut-off date, and all efficacy data are determined by a blinded, independent central review (BICR) of each patient’s tumor scan.

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"We are highly encouraged by the robust efficacy signal and favorable safety profile observed with onvansertib plus standard-of-care from the first 30 evaluable patients in our randomized first-line RAS-mutated mCRC CRDF-004 trial," said Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. "Our data shows an objective response rate of 64% in patients receiving the 30 mg dose of onvansertib in combination with standard of care, significantly higher than the 33% objective response rate observed in the control arms of standard of care alone. In addition, as can be seen in the spider plots, we are observing deeper tumor response in patients receiving the 30mg dose of onvansertib compared to those receiving the 20mg dose with similar safety profiles for both doses."

Study Design

The CRDF-004 phase 2 trial is currently enrolling patients with mCRC who have a documented KRAS or NRAS mutation. Onvansertib is added to SoC consisting of FOLFIRI plus bevacizumab or FOLFOX plus bevacizumab. Patients are being randomized in a 1:1:1 ratio to either 20mg of onvansertib plus SoC, 30mg of onvansertib plus SoC, or SoC alone. The primary endpoint is objective response rate (ORR), and the secondary endpoints include progression-free survival (PFS), duration of response (DOR) and safety.

Efficacy Data

Objective Response Rates observed in the CRDF-004 clinical trial, as of the data cut-off date of November 26, 2024, are shown below.

Control Arm

(SoC alone)

20mg dose of onvansertib + SoC

30mg dose of onvansertib + SoC

All onvansertib patients

33% ORR

(3 of 9)

50% ORR

(5 of 10)

64% ORR

(7 of 11)

57% ORR

(12 of 21)

Spider Plots, displaying the change in tumor size from baseline for each patient over time, demonstrate deeper responses observed in patients receiving the 30mg dose of onvansertib in combination with the SoC compared to both the control arms and 20mg dose of onvansertib arms.

Safety and Tolerability

Onvansertib in combination with chemo/bevacizumab was well-tolerated and there have been no major or unexpected toxicities observed.

"Overall, these data support our belief that onvansertib has potential to change the treatment paradigm for the entire first-line RAS-mutated mCRC patient population of almost 50,000 new patients diagnosed in the U.S. annually," said Mark Erlander, Chief Executive Officer of Cardiff Oncology. "In addition to the efficacy signal observed, the data demonstrate that onvansertib can safely be combined with the two different chemo backbones that are currently approved as standard of care in the first-line setting, thus providing a key differentiated profile over previous generation PLK1 inhibitors. We look forward to providing additional clinical updates from our CRDF-004 trial in the first half of 2025."

Upcoming expected milestones

•
Additional clinical data from CRDF-004 trial expected in 1H 2025

Conference Call and Webcast

Cardiff Oncology will host a conference call and live webcast at 8:00 a.m. ET / 5:00 a.m. PT on December 10, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the "Events" section of the company’s website. A webcast replay will be available in the investor relations section on the company’s website following the completion of the call.

On December 10, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, reported that it has released the latest clinical data from a global study of its novel drug candidate, olverembatinib (HQP1351), in patients with heavily pretreated chronic myeloid leukemia (CML), in a Poster Presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in San Diego, CA, the United States (Press release, Ascentage Pharma, DEC 10, 2024, View Source;1-5-year-follow-up-data-from-a-global-study-of-olverembatinib-reaffirms-potential-in-overcoming-resistanceintolerance-to-ponatinib-or-asciminib-302327550.html [SID1234649007]). Prof. Hagop Kantarjian, MD, and Prof. Elias Jabbour, MD, from the Department of Leukemia, The University of Texas MD Anderson Cancer Center, are the principal investigators of the study.

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The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH (Free ASH Whitepaper) Annual Meeting. Furthermore, this is the seventh consecutive year for studies of olverembatinib to be selected for Oral Reports at the meeting.

After releasing the preliminary results from the global study of olverembatinib in an Oral Report at ASH (Free ASH Whitepaper) 2022 and the updated results from a larger patient sample at ASH (Free ASH Whitepaper) 2023, this year Ascentage Pharma presented the 1.5-year follow-up data in patients with heavily pretreated CML-CP. In the latest data, olverembatinib showed strong, durable and consistent antileukemic activity, the ability to overcome resistance/intolerance to the third-generation tyrosine kinase inhibitor (TKI) ponatinib or the allosteric STAMP inhibitor asciminib, as well as favorable tolerability in patients with heavily pretreated CML-CP.

As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib has already been approved for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant CP-CML or accelerated-phase (AP-) CML harboring the T315I mutation; and adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. In January 2024, olverembatinib was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III trial in previously treated adult patients with CML-CP.

Prof. Elias Jabbour commented, "Olverembatinib is a very promising next-generation TKI, and existing data demonstrate its therapeutic ability in patients with resistant/intolerant to ≥2 TKIs CP-CML and above. The high response rate that Olverembatinib has shown in Ponatinib or Asciminib failed patients is encouraging. We continue to recruit for the global Phase III trial examining this novel therapy."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "The latest data from this global study further demonstrated olverembatinib’s therapeutic potential in patients with drug-resistant CML, including those who had failed prior treatment with ponatinib and asciminib, and once again underscored the drug candidate’s promise in addressing an unmet global clinical need in CML. At Present, a global registrational Phase III study of olverembatinib has been cleared by the US FDA and is already ongoing. We hope, in not too distant future, this innovative drug will become accessible to patients worldwide who are in desperate need of novel therapies. Fulfilling our founding mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates such as olverembatinib to bring more safe and effective therapies to patients as soon as possible."

Highlights of the data this study reported at ASH (Free ASH Whitepaper) 2024 are as below:

Olverembatinib (HQP1351) Overcomes Resistance/Intolerance to Asciminib and Ponatinib in Patients (pts) with Heavily Pretreated Chronic-Phase Chronic Myeloid Leukemia (CP CML): A 1.5-Year Follow-up Update with Comprehensive Exposure-Response (E-R) Analyses

Format: Poster Presentation

Abstract#: 3151

Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II

Highlights:

Introduction: New treatment options are needed for patients with CP-CML resistant/intolerant to third-generation (3G) TKI ponatinib and/or asciminib, a specifically targeting the ABL myristoyl pocket (STAMP) inhibitor. Olverembatinib is a well-tolerated TKI with potential to overcome resistance. This update presents efficacy and safety data of olverembatinib in patients with heavily pretreated CP-CML.

Enrolled Patients and Study Methods:

Adults with CP-CML previously treated with ≥2 TKIs and/or a STAMP inhibitor, adequate organ function, and no major molecular response (MMR) were eligible.
As of July 28, 2024, 67 pts with CP-CML were enrolled; median (range) follow-up was 74.3 (0.1-217.1) weeks; median (range) age, 50 (21-80) years; and 38 (56.7%) patients were male.
Patients were randomly allocated to receive olverembatinib at doses of 30, 40, or 50 mg orally every other day (QOD) in 28-day cycles, with stratification based on T315I mutation status. Comprehensive E-R analyses were performed.
Efficacy Results:

No patient had efficacy at baseline. 35 of 60 (58.3%) evaluable patients achieved CCyR and 29/64 (45.3%) achieved MMR. At 12 months, the overall MMR rate was 61.4% (27/44). CCyR was achieved by 66.7% of patients with the T315I mutation vs 54.8% without it, and MMR was achieved by 50.0% vs 43.5%, respectively.
Of 28 cytogenetic response-evaluable patients with ponatinib-failed CP-CML, 15 (53.6%) achieved CCyR. The CCyR rates in patients with prior ponatinib resistance and intolerance were 52.2% (12/23) and 75.0% (3/4), respectively. In the 30 molecular response-evaluable patients who were previously treated with ponatinib, 12 (40.0%) achieved MMR, including 47.8% (11/23) of those with prior resistance and 16.7% (1/6) with intolerance. No patient above had efficacy at baseline.
In evaluable patients with asciminib treatment failure, 37.5% (6/16) achieved CCyR and 30% (6/20) achieved MMR, including a CCyR rate of 30.8% (4/13) and an MMR rate of 26.7% (4/15) in those with prior resistance, and a CCyR rate of 50.0% (1/2) and an MMR rate of 25.0% (1/4) in those with intolerance. No patient had efficacy at baseline.
Safety Results: Among 66 subjects receiving olverembatinib, a total of 62 (93.9%) reported treatment-emergent adverse events (TEAEs) of any grade, with 44 (66.7%) experiencing grade ≥ 3 TEAEs. In addition, 60 (90.9%) patients reported TRAEs of any grade. Common TRAEs (≥20%) were elevated creatine phosphokinase (37.9%), thrombocytopenia (24.2%), and increased alanine aminotransferase (22.7%).

Conclusions: Olverembatinib was well tolerated and showed strong and durable antileukemic activity in patients with heavily pretreated CP-CML. The registrational study is recruiting.

On December 10, 2024 Evariste, a TechBio using mathematics and AI to design small molecule therapeutics, reportedto have entered into a preclinical research agreement with Orion Corporation, a leading Finnish pharmaceutical company (Press release, Orion, DEC 10, 2024, View Source [SID1234649023]).

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As part of the agreement, Evariste will use its innovative discovery platform, Frobenius Discovery, to design small molecule inhibitors for a target selected by Orion. The collaboration will deploy Frobenius Discovery’s full suite of proprietary machine learning algorithms, automated compound designers, and accelerated free energy calculations to deliver potential candidate molecules.

"We are excited to work together with Evariste in utilizing cutting-edge AI-driven molecular design and mathematical algorithms to accelerate our drug discovery process," said Emilia Väisänen, Head of Medicinal Chemistry at Orion.

Anna Hercot, CEO of Evariste, commented: "We are very excited to leverage the Frobenius Discovery platform and work with an outstanding team at Orion to help accelerate the delivery of new medicines to patients."

On December 10, 2024 Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) (the "Company"), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it has drawn down the final tranche of €5 million ("Tranche C") under the credit facility agreement for up to €40 million entered into with the European Investment Bank (the "EIB) on December 28, 2022 (the "Finance Contract") (Press release, Cellectis, DEC 10, 2024, View Source [SID1234648976]). With the drawdown of Tranche C, the Company has drawn down the full €40 million available under the Finance Contract. Tranche C is expected to be disbursed by the EIB by December 18, 2024. The Company plans to use the proceeds of Tranche C towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22 and UCART20x22.

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As a condition to the disbursement of Tranche C the Company issued 611,426 warrants to the benefit of the EIB, in accordance with the terms of the 14th resolution of the shareholders’ meeting held on June 28, 2024 and articles L. 228-91 and seq. of the French Commercial Code (the "Tranche C Warrants").

Each Tranche C Warrant allows the EIB to subscribe for one ordinary share of the Company, at a price of €1.70, corresponding to 99% of the volume-weighted average price of the Company’s ordinary shares over the last 3 trading days preceding the decision of the board of directors of the Company to issue the Tranche C Warrants. The total number of shares issuable upon exercise of the Tranche C Warrants represent circa 0.6% of the Company’s outstanding share capital as at their issuance date.

Tranche C will mature six years from its disbursement date and will accrue interest at a rate of 6% per annum capitalized annually and payable at maturity.

The other terms of the Tranche C Warrants and prepayment events of Tranche C under the Finance Contract are as set forth in the Company’s press release of April 4, 2023 and Form 6-K filed with the U.S. Securities and Exchange Commission on such date.

On December 9, 2024 Protara Therapeutics, Inc. (Nasdaq: TARA) ("Protara"), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported the pricing of its underwritten public offering of 13,690,000 shares of its common stock at a price to the public of $6.25 per share and pre-funded warrants to purchase 2,325,372 shares of common stock at a price of $6.249 per pre-funded warrant, which represents the per share price for the common stock less the $0.001 per share exercise price for each such pre-funded warrant (Press release, Protara Therapeutics, DEC 10, 2024, View Source [SID1234648992]). In addition, Protara has granted the underwriters a 30-day option to purchase up to an additional 2,402,305 shares of common stock at the public offering price, less underwriting discounts and commissions. All shares and pre-funded warrants in the offering are being sold by Protara. The gross proceeds from the offering are expected to be approximately $100 million before deducting underwriting discounts and commissions and offering expenses payable by Protara and excluding any exercise of the underwriters’ option to purchase additional shares and the exercise of any pre-funded warrants. The offering is expected to close on December 11, 2024, subject to satisfaction of customary closing conditions. Protara intends to use the net proceeds received from the offering to fund the clinical development of TARA-002, as well as the development of other clinical programs. Protara may also use the net proceeds from the offering for working capital and other general corporate purposes.

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TD Cowen, Cantor, LifeSci Capital, Oppenheimer & Co. and Scotiabank are acting as joint book-running managers of the offering.

The shares of common stock and the pre-funded warrants will be issued pursuant to an effective shelf registration statement on Form S-3 (File No. 333-275290) that was declared effective on November 14, 2023 by the U.S. Securities and Exchange Commission (the "SEC"). The offering is being made only by means of a prospectus supplement and the accompanying prospectus. A final prospectus supplement relating to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may be obtained from the offices of TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by email at [email protected] or by telephone at (855) 495-9846; Cantor Fitzgerald & Co., 110 East 59th Street, 6th Floor, New York, New York 10022, Attention: Capital Markets, or by email at [email protected]; or LifeSci Capital LLC, 1700 Broadway, 40th Floor, New York, New York 10019, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the applicable securities laws of such state or jurisdiction.