On June 20, 2024 4 Redx Pharma (JPJ:REDX), the clinical-stage, small molecule biotechnology company,
reported that Phase 2 data from zamaporvint (RXC004), a Porcupine inhibitor targeting Wnt-ligand dependent GI cancers, will be presented at the European Society for Medical Oncology Gastrointestinal Cancers Congress (ESMO GI), 26-29th June, Munich, Germany (Press release, Redx Pharma, JUN 20, 2024, View Source [SID1234644454]).

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Zamaporvint is a potent, selective, orally-active Porcupine inhibitor in development for hard-to-treat GI cancers. The principal efficacy hypothesis for zamaporvint is for use in combination, which has been investigated in Phase 2 signal searching patient cohorts with anti-PD-1 therapy. Monotherapy for single agent activity has also been investigated. The PORCUPINE study was in genetically-selected patients with microsatellite stable metastatic colorectal cancer (MSS mCRC) as monotherapy and immuno-oncology combination (clinicaltrials.gov NCT04907539). The PORUPINE2 study was in all-comers biliary tract cancer as monotherapy and immuno-oncology combination, and in genetically selected pancreatic cancer as monotherapy (clinicaltrials.gov NCT04907851).

The data will be presented in two posters, one on the PORCUPINE study and one on the PORCUPINE2 study. Notably, these data demonstrate that zamaporvint, in combination with an anti-PD-1 agent in genetically-selected patient populations has the potential to improve upon efficacy outcomes achieved with standard of care alone.
Details of the poster presentations are as follows:

1)
Abstract Title: Phase 2 results of the Porcupine (PORCN) inhibitor zamaporvint
(RXC004) in genetically selected microsatellite stable colorectal
cancer patients
Session Title: Poster Session
Date/Time: Thursday 27 June 3:35 – 4:30pm CEST
Poster Number: 37P

2)
Abstract Title: Phase 2 results of the porcupine (PORCN) inhibitor zamaporvint
(RXC004) in patients with pancreatic and biliary tract cancer
Session Title: Poster Session
Date/Time: Thursday 27 June 3:35 – 4:30pm CEST
Poster Number: 391P
A copy of the posters will be made available on Company’s website following the presentation at:
View Source

On June 20, 2024 CellxLife reported that Eric von Hofe, Ph.D., will serve as the company’s first Chief Executive Officer (Press release, CellXLife, JUN 20, 2024, View Source [SID1234644470])There are currently very few treatment options for children suffering from metastatic Ewing sarcoma or osteosarcoma. The most common treatment is surgical removal of the tumors in combination with radiation and chemotherapy. For children with recurring metastatic Ewing sarcoma or osteosarcoma, the 5-year survival rate is usually 20-30% and in the U.S., approximately $750,000 is spent on treatment over the course of a patient’s life. i,ii

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"Ewing sarcoma and osteosarcoma are devastating diseases that have far-reaching impact, particularly in pediatric patients and their caregivers," said Dr. von Hofe. "I am honored to join the CellxLife team to help advance efforts in bringing this promising new biotherapeutic to the thousands of children and families fighting these cancers globally."

Through CellxLife’s proprietary platform, dendritic cells are taken from the body and presented with the patient’s own tumor cell antigens, then re-administered back into the body as an immunotherapeutic vaccine to educate the immune system. Study data generated to date has indicated that this both activates immune cells to attack remaining cancer cells in the body and shapes the immunological memory to greatly reduce the chances of cancer recurrence. In a prior Phase 1 study, 75% of pediatric participants diagnosed with metastatic Ewing’s or osteosarcoma, who responded well to surgery, overcame their cancer, and are still alive today. Out of all the participants in the trial, 62.5% of children with metastatic osteosarcoma who were treated with the dendritic cell-based therapy lived for more than 15 years.

The CellxLife clinical team believes the therapy can cross over to other solid tumors, such as ovarian, breast, colorectal, pancreatic, glioblastoma, lung, and other solid tumors. The principle is the same; once a tumor is removed, the vaccine will shape the immunological memory of the cancer cells in the lymph nodes and greatly reduce the chances of cancer recurrence.

"This could be a breakthrough for anyone who is faced with the horrible realization that cancer could reoccur after their tumor is removed," said Ruvin Orbach, founder of CellxLife. "It’s an honor to have Eric on board as CEO at this important time of growth for CellxLife. We are committed to building the team and raising the capital required to further advance this de-risked therapeutic candidate. We are currently planning the Phase II trials with an orphan designation and significantly reducing the regulatory pathway for this promising immunotherapy."

Dr. von Hofe has over 30 years of experience in managing and overseeing biotechnology programs, with a focus on cancer immunotherapy and technology development. Most recently he led development efforts at AffyImmune Therapeutics where he oversaw the clinical development and orphan designation for a novel CAR-T cell therapeutic targeting refractory thyroid cancer. Previously, he was at Antigen Express where he led the development of an immunotherapeutic vaccine for breast and prostate cancer, resulting in a collaboration with Merck. Prior to that, he worked at Millennium Pharmaceuticals first as Program Director for Target Validation and later as Director of Programs & Operations, Discovery Research. Previously, Dr. von Hofe was Director, New Targets at Hybridon, Inc., where he coordinated in-house and collaborative research that validated gene targets for novel antisense medicines. Dr. von Hofe also held the position of Assistant Professor of Pharmacology at the University of Massachusetts Medical School, where he received a National Cancer Institute Career Development Award for defining mechanisms by which alkylating carcinogens create cancers. He received his Ph.D. in Experimental Pathology from the University of Southern California and was a postdoctoral fellow at both the University of Zurich and Harvard University School of Public Health.. The company was formed in late 2023 to advance a dendritic cell-based therapeutic vaccine candidate that aims to expand treatment options for children with recurring metastatic Ewing sarcoma and osteosarcoma.

On June 20, 2024 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) (the "Company" or "Sonnet"), a clinical-stage company developing targeted immunotherapeutic drugs, reported the entry into a definitive agreement for the immediate exercise of certain outstanding warrants to purchase up to an aggregate of 2,828,500 shares of common stock, issued by Sonnet in October 2023 (the "Existing Warrants"), at a reduced exercise price of $1.20 per share (Press release, Sonnet BioTherapeutics, JUN 20, 2024, View Source [SID1234644455]). The shares of common stock issuable upon exercise of the Existing Warrants are registered pursuant to an effective registration statement on Form S-1 (File No. 333-274581). The closing of the offering is expected to occur on or about June 21, 2024, subject to satisfaction of customary closing conditions.

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Ladenburg Thalmann & Co. Inc. is acting as the exclusive placement agent for the offering.

In consideration for the immediate exercise of the Existing Warrants for cash, Sonnet will issue new unregistered warrants to purchase up to 5,657,000 shares of common stock (the "New Warrants"). The New Warrants will have an exercise price of $1.55 per share (priced at-the-market under the rules of the Nasdaq Stock Market), will be exercisable upon issuance, and have a term equal to five years from the date of issuance. In connection with the transaction, Sonnet also (i) reduced the exercise price of the Existing Warrants to purchase an aggregate of 2,824,000 shares of common stock for all holders not participating in the transaction to $1.20 per share for the remaining term of the Existing Warrants, (ii) reduced the exercise price of certain outstanding warrants to purchase up to an aggregate of 227,272 shares of common stock issued by Sonnet in June 2023 (the "June Warrants") to $1.55 per share and (iii) extended the term of the June Warrants to the term of the New Warrants.

The gross proceeds to Sonnet from the exercise of the Existing Warrants are expected to be approximately $3.4 million, prior to deducting placement agent fees and offering expenses. The Company intends to use the net proceeds for research and development, including clinical trials, working capital, the repayment of all or a portion of liabilities, and general corporate purposes.

The New Warrants described above were offered in a private placement pursuant to an applicable exemption from the registration requirements of the Securities Act of 1933, as amended (the "1933 Act"), and, along with the shares of common stock issuable upon exercise, have not been registered under the 1933 Act, and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission ("SEC") or an applicable exemption from such registration requirements. Sonnet has agreed to file a registration statement with the SEC covering the resale of the shares of common stock issuable upon exercise of the New Warrants.

This press release does not constitute an offer to sell or a solicitation of an offer to buy the securities in this offering, nor shall there be any sale of these securities in any state or other 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 other jurisdiction.

On June 20, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported new positive data from the ongoing global randomized Phase 1b/2 clinical study in which amezalpat2 (TPST-1120), Tempest’s PPAR⍺ antagonist, delivered a six-month improvement in median overall survival ("OS") advantage when combined with atezolizumab and bevacizumab in a comparison to atezolizumab and bevacizumab alone in the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma ("HCC") (Press release, Tempest Therapeutics, JUN 20, 2024, View Source [SID1234644456]).

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"We are thrilled by these new survival data that build on the already meaningful data released in the fall showing the improvement of the amezalpat arm over atezolizumab and bevacizumab control across all study endpoints," said Stephen Brady, president and chief executive officer of Tempest. "These new data come after 10 more months of follow-up since the last data analysis and show not only a strong hazard ratio of 0.65 favoring the amezalpat arm, but also a six-month improvement in the median overall survival with half the patients still in survival follow up, as well as observation of a survival advantage across key populations – results that we believe put amezalpat in a strong position for a successful pivotal Phase 3."

At the cutoff date of February 14, 2024, the new data from 40 patients randomized to the amezalpat arm and 30 patients randomized to the control arm show:

21 month median OS for the amezalpat arm versus 15 month for the control arm, a six-month survival advantage
20/40 patients remain in survival follow up in the amezalpat arm, compared to 9/30 patients in the control arm
0.65 hazard ratio ("HR") for OS, revealing a stable HR since the top-line analysis 10 months earlier when the HR was 0.59
Manageable safety profile consistent with Phase 1 data
The earlier top-line data analysis, dated April 20, 2023, had a median follow up of 9.2 and 9.9 months for the amezalpat and control arms, respectively, and showed:

Confirmed objective response rate ("cORR" or "confirmed ORR") of 30% for the amezalpat arm versus 13.3% for the control arm;
Biomarker subpopulation findings were consistent with the mechanism of action of amezalpat
Patients with b-catenin activating mutations (21% in this study (n=7)) showed a cORR of 43% and a disease control rate ("DCR") of 100% in the amezalpat arm
The amezalpat arm was consistently active across both PD-L1 positive and PD-L1 negative tumors, with a cORR of 27% in the amezalpat arm compared to 7% for the control arm in PD-L1 negative tumors
Amezalpat remains well tolerated, with safety data comparable between the two arms
The randomized arms were generally well balanced at baseline
ORR was determined by RECIST v1.1, and confirmed responses included at least two scans. Tempest retains all product rights to amezalpat.

Conference Call & Webcast Information

Tempest will host a webcast conference call today, June 20, 2024 at 8:30am ET.

To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the investor section of the Tempest website at View Source The webcast will be available for replay for 30 days.

About the Randomized Clinical Trial

The Phase 1b/2 global randomized HCC study is part of Roche’s Morpheus program and evaluates amezalpat in combination with atezolizumab and bevacizumab versus atezolizumab and bevacizumab, the standard of care, in patients with unresectable or metastatic HCC not previously treated with systemic therapy. The trial randomized 70 patients to receive either amezalpat with atezolizumab + bevacizumab or a contemporaneous control arm of atezolizumab + bevacizumab alone at approximately 25 sites worldwide, including in the United States, Europe, and Asia. The primary efficacy endpoint was confirmed objective response rate, and key secondary endpoints including PFS and OS. Under the terms of the clinical collaboration agreement, Roche is managing the study operations for this global, multicenter trial and Tempest retains all product rights.

About Amezalpat (TPST-1120)

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s data suggest that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In an ongoing global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors.

About Hepatocellular Carcinoma

HCC is an aggressive cancer with rising mortality and is projected to become the third leading cause of cancer death by 2030.3 Every year, more than 900,000 people worldwide are diagnosed with HCC.4 Incidence and mortality are highest in East Asia and are increasing in parts of Europe and the US.5 In the US, HCC represents the fastest-rising cause of cancer-related death.3

Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.6

Even if diagnosed in the early stage, an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery.7 Early recurrence is associated with poorer prognosis and shorter survival.5,8 Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.

On June 20, 2024 Medigene AG (Medigene, the "Company", FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, reported that it has selected its lead candidate for MDG2021, a T cell receptor engineered T cell (TCR-T) therapy targeting Kirsten rat sarcoma viral oncogene homologue (KRAS) G12D with human leukocyte antigen (HLA)-A*11 being developed in combination with the Company’s PD1-41BB costimulatory switch protein (CSP) technology (Press release, MediGene, JUN 20, 2024, View Source [SID1234644457]).

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With its proprietary End-to-End (E2E) Platform, the Company has successfully generated an optimal KRAS G12D-HLA-A*11 TCR that meets the Company’s selection criteria for highly specific, sensitive and safer (3S) TCRs as the lead that will now advance into the pre-clinical stage. The Company’s evaluation criteria for TCR selection included sensitive and precise tumor cell recognition combined with simultaneous display of a high safety profile demarked by lack of recognition of panels of healthy cells and tissues, matched and mismatched for HLA.

"We are delighted to announce that we have successfully generated a novel 3S TCR targeting KRAS G12D-A*11 that meets our rigorous selection criteria of high specificity, heightened sensitivity, and promising potential for enhanced safety," said Dr. Selwyn Ho, Chief Executive Officer at Medigene.

"The selection of this KRAS G12D lead-TCR expands our library of TCRs against neoantigens and cancer-testis antigens. Further, with the addition of our armoring & enhancement technology, PD1-41BB CSP to our TCR-T therapies, we are confident that our approach will yield best-in-class TCR-T therapies, providing improved outcomes for patients with to date, difficult-to-treat solid tumors such as colorectal cancer and pancreatic cancer. We are looking forward to presenting initial pre-clinical data on MDG2021 at upcoming scientific conferences in the second half of 2024."

The Company’s E2E Platform continues to generate 3S TCRs with unique and distinctive attributes that will be utilized across multiple therapeutic modalities, including TCR-T therapies, TCR-guided T cell engagers and TCR natural killer cell therapies. The new 3S TCR is designed for co-expression with Medigene’s PD1-41BB CSP to enhance the proliferation, persistence, and cytotoxic function of TCR-T cells, while simultaneously mitigating immunosuppressive effects of the tumor microenvironment.

Following the lead announcement of Medigene’s first KRAS program MDG2011 (KRAS G12V-A*11) in June 2023, MDG2021 is the latest program now in preclinical development within Medigene’s library of neoantigens that comprises multiple KRAS mutations and HLAs. The MDG20xx program is dedicated to further develop the Company’s TCR library, exploring other KRAS neoantigen mutations and HLAs.