On March 8, 2023 Redx (AIM:REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease, reported topline monotherapy data from the biliary tract cancer (BTC) module of the RXC004 PORCUPINE2 Phase 2 clinical trial programme (Press release, Redx Pharma, MAR 8, 2023, View Source [SID1234628337]).

RXC004 is an orally active, once daily, porcupine inhibitor being developed as a targeted treatment for Wnt-ligand dependent cancers. The objective of the Phase 2 programme is to provide an initial assessment of the efficacy and safety of the drug both as a single agent and in combination with anti-PD-1 therapy, in patients with certain Wntligand dependent solid tumours whose cancers have progressed following standard of care therapies. The RXC004 Phase 2 clinical development programme consists of two studies, PORCUPINE and PORCUPINE2, which are detailed below.

The data announced today, the first from the Phase 2 programme, are from 16 previously treated patients enrolled in the advanced BTC monotherapy arm of the PORCUPINE2 study. The primary endpoint was Progression Free Survival at six months. Some patients received durable clinical benefit from RXC004 in this cohort, consistent with clinical activity seen in the Phase 1 trial, and the safety profile of RXC004 in this module was also consistent with the safety data previously reported in the Phase 1 trial. However, the overall results are not sufficient to support the further development of RXC004 as a monotherapy in this treatment setting.

Planned retrospective analysis of all efficacy and biomarker data in this BTC monotherapy cohort will increase the understanding of the single agent activity of RXC004 and will be used to aid interpretation of the ongoing combination module efficacy, where RXC004 is used alongside anti-PD-1 therapy, pembrolizumab.

"Our Phase 2 program is designed to explore the activity of RXC004 both as monotherapy and in combination with immune checkpoint inhibitors, consistent with its postulated dual mechanism of action. Our primary efficacy hypothesis is that in combination it can overcome immune evasion and anti-PD-1 resistance, which could open new patient segments," said Dr Jane Robertson, Chief Medical Officer, Redx Pharma. "While today’s results do not support further clinical development of RXC004 as monotherapy in recurrent BTC, where very few drugs have received regulatory approval as single agents in this hard-to-treat disease, they are nonetheless consistent with the overall hypothesis that RXC004 has potential as an active component of combination therapy. We look forward to the data read out from the combination module with pembrolizumab, that is expected in the second half of this year."

Biliary tract cancer, a cancer with an annual incidence of 51,000 patients1, has an extremely poor prognosis, with only a 2% 5-year survival rate2 and a treatment response rate of less than 5% with standard second-line chemotherapy.

About the RXC004 Phase 2 Clinical Trial Program
The first study in the Phase 2 programme, PORCUPINE, (clinicaltrials.gov NCT04907539) is focused on patients with advanced microsatellite stable metastatic colorectal cancer (MSS mCRC) that has not progressed following treatment with standard of care and is evaluating preliminary efficacy and safety of RXC004 in genetically selected patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, advanced MSS mCRC. A second Phase 2 study of RXC004, PORCUPINE2, (clinicaltrials.gov NCT04907851), for genetically selected pancreatic cancer and biliary cancer, a highly Wnt-ligand dependent cancer is also ongoing.

Given the dual mechanism of action of RXC004, which preclinically was shown to inhibit tumour growth and immune evasion, there is a strong rationale for immune therapy combination. In November 2022, Phase 1 clinical data evaluating the safety and tolerability of RXC004 in combination with nivolumab, in patients with advanced malignancies was presented as a poster at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference. The data was suggestive of an anti-tumour immune response, which is reported to correlate with an improved response to anti-PD-1 immune checkpoint inhibitors. The results of the study supported a dose selection of 1.5mg once daily to be used in combination modules of both PORCUPINE and PORCUPINE2.

The combination module of the PORCUPINE trial will evaluate RXC004 in combination with nivolumab, (OPDIVO – Bristol Myers Squibb, a PD-1 inhibitor) in MSS mCRC and this module is now open for recruitment in all countries taking part in the trial including the US and the UK. The combination module of the PORCUPINE2 study, (clinicaltrials.gov NCT04907851), will evaluate RXC004 in combination with pembrolizumab, (KEYTRUDA – MSD’s anti-PD-1 therapy) in biliary tract cancer. A clinical trial supply and collaboration agreement was entered into with MSD (Merck & Co., Inc., Rahway, NJ, USA) in December 2022 for the supply of KEYTRUDA, and this module is open for recruitment in all countries taking part in this clinical trial including the UK and Australia.

The person responsible for the release of this announcement on behalf of the Company is Claire Solk, Company Secretary.

For further information, please contact:

Redx Pharma Plc T: +44 (0)1625 469 918
UK Headquarters
Caitlin Pearson, Head of Communications [email protected]

Lisa Anson, Chief Executive Officer

US Office
Peter Collum, Chief Financial Officer

SPARK Advisory Partners (Nominated Adviser) T: +44 (0)203 368 3550
Matt Davis/ Adam Dawes

WG Partners LLP (Joint Broker) T: +44 (0)203 705 9330
Claes Spång/ Satheesh Nadarajah/ David Wilson

Panmure Gordon (UK) Limited (Joint Broker) T: +44 (0)207 886 2500
Rupert Dearden/ Freddy Crossley/ Emma Earl

FTI Consulting T: +44 (0)203 727 1000
Simon Conway/ Ciara Martin

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On March 8, 2023 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that it has entered into an agreement to sell its royalty interest on future global net sales of TZIELD (teplizumab-mzwv) to a wholly-owned subsidiary of DRI Healthcare Trust for up to $200 million (Press release, MacroGenics, MAR 8, 2023, View Source [SID1234628336]). MacroGenics retains its other economic interests related to TZIELD, including future potential regulatory and commercial milestones.

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Under the terms of the agreement with DRI, MacroGenics will receive a $100 million upfront payment for the sale of its single-digit royalty on global net sales of TZIELD. MacroGenics will have the right to receive a 50% share of the royalty on global net sales above a certain annual threshold. In addition, the Company is eligible to receive up to $50 million from DRI upon the occurrence of pre-specified events tied to the advancement of TZIELD for the treatment of newly diagnosed type 1 diabetes. The Company may also receive an additional $50 million if TZIELD achieves a certain level of net sales.

On March 8, 2023 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported that the first two patients were enrolled and treated today in its pivotal multicenter trial, known as the ReSTART trial (Recurrent SCC Treatment with Alpha DaRT Radiation Therapy), for the treatment of recurrent cutaneous squamous cell carcinoma (cSCC) (Press release, Alpha Tau Medical, MAR 8, 2023, View Source [SID1234628334]). The patients were treated at the University Cancer Center in Houston, Texas

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The trial is intended to enroll up to 86 participants who have biopsy-proven recurrent cSCC who are not otherwise indicated for surgery or standard radiation therapy, and for whom no curative systemic treatment is available. The primary study endpoints include overall objective response rate, based on best overall response, duration of response at 6-months from initial observation of a response to Alpha DaRT insertion, and safety of the Alpha DaRT treatment. The study’s secondary objectives are to assess the progression-free survival and overall survival at 1-year following Alpha DaRT treatment, overall duration of response, local control, and quality of life. Additional information about the trial can be found at View Source

Alpha Tau CEO Uzi Sofer commented, "Today marks an important milestone for the Company and paves our path forward towards our ultimate goal of U.S. regulatory approval. Moreover, being able to enroll the first two patients simultaneously in one site demonstrates the high unmet need in this patient population and is an important boost in our recruitment efforts. We are hopeful that the results of this study, together with the Breakthrough Device Designation from the FDA for the treatment of this indication, will allow us to gain FDA approval and make the Alpha DaRT treatment available as quickly as possible for patients who suffer from recurrent cSCC. In the coming year, we will continue to focus our efforts on three main areas: swift recruitment in the ongoing ReSTART study, targeting initial results from our internal organ clinical program such as the treatment of pancreatic and prostate cancers, and continued scale-up of our production capacity to allow for smooth and efficient production

We remain committed to bringing new hope to patients in this very difficult to treat population. We would like to thank Dr. Mark D’Andrea and Dr. Lawrence Clarke and the dedicated staff at University Cancer Center in Houston for enrolling and treating the first patients in the ReSTART trial and look forward to the forthcoming results," said Alpha Tau Chief Medical Officer, Dr. Robert Den

Dr. Mark A. D’Andrea, radiation oncologist at University Cancer Center in Houston, commented, "I believe that Alpha DaRT can be a real breakthrough in the treatment of recurrent cSCC. These patients have exhausted the effective treatment options available to them, and Alpha DaRT may give these patients additional hope for a successful outcome. In my experience as a radiation oncologist, treatment with the Alpha DaRT is a quick and straightforward procedure that can often be done in the office setting or procedure room in the clinic without the need for hospitalization or a shielded radiation suite. The procedure is often done using a local anesthetic, with the patient returning after 2 weeks for removal of the sources. The patient should then be able to return to a normal daily routine quickly."

On March 8, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported that Mark Rothera, its President and Chief Executive Officer, and Lisa Rojkjaer, M.D., its Chief Medical Officer, are scheduled to participate in a virtual fireside chat at the 33rd Annual Oppenheimer Healthcare Conference on Wednesday, March 15, 2023, at 12:00 p.m. ET (Press release, Viracta Therapeutics, MAR 8, 2023, View Source [SID1234628332]).

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A live webcast of the fireside chat will be available on the Investors section of the Viracta website under "Events and Webcasts" and archived for 30 days.

On March 8, 2023 TRACON Pharmaceuticals, Inc. (Nasdaq: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported financial results for the fourth quarter and year ended December 31, 2022 (Press release, Tracon Pharmaceuticals, MAR 8, 2023, View Source [SID1234628331]). The Company will host a conference call and webcast today at 4:30 PM Eastern Time / 1:30 PM Pacific Time

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The significant progress we achieved in the fourth quarter sets up 2023 to be a potentially transformational year for TRACON," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "In December we announced interim efficacy results from the ongoing ENVASARC pivotal trial demonstrating that envafolimab achieved a double-digit objective response rate, both as a single agent and in combination with Yervoy, in 36 patients with refractory sarcoma. We also secured a non-dilutive non-recourse financing of up to $30 million related to the I-Mab arbitration award decision which we expect this month, of which $3.5 million was funded in December. Importantly, accrual in ENVASARC remains ahead of projections and we expect the second and final interim efficacy analysis of 92 patients in the third quarter, after each patient has had two on-study scans, and to complete accrual before year end, leading to final data in 2024

Recent Corporate Highlights

In November 2022, we announced dosing of the first patient in a Phase 1/2 trial that studies envafolimab with our proprietary CTLA-4 antibody YH001 in combination with doxorubicin in front line sarcoma

In November 2022, we completed the Phase 1 study of the CD73 antibody TJ4309, triggering I-Mab’s right to reacquire the asset for a payment to TRACON of $9M

In December 2022, we announced positive interim results in the ENVASARC Phase 2 pivotal trial based on a double-digit objective response rate (ORR) by central radiographic review in the cohort of single agent envafolimab (N=18) and the cohort of envafolimab given in combination with Yervoy (N=18). The primary endpoint of the pivotal ENVASARC trial is achievement of an 11.25% ORR by central radiographic review in either 80 patient cohort

In December 2022, we announced a non-recourse non-dilutive financing of up to $30M related to the arbitration with I-Mab. We received $3.5M up front and the remainder will be available subject to the award exceeding a threshold and satisfaction of other conditions.

Expected Upcoming Milestones

Report the binding decision of the International Chamber of Commerce Arbitration Panel on the ongoing arbitration involving the TJ4309 and bispecific antibody agreements with I-Mab Biopharma where we are seeking to recover over $200 million in damages, which we expect in the first quarter of 2023

Report the second and final interim efficacy analysis from the ENVASARC pivotal trial following the review of more than 12 weeks of efficacy data (including two on-study CT scans) by the independent data monitoring committee from 46 patients who receive envafolimab as a single agent and 46 patients who receive envafolimab in combination with Yervoy, which we expect in the third quarter of 2023

Complete full accrual of the ENVASARC pivotal trial before the end of 2023

Report Phase 1 data from the Phase 1/2 clinical trial of YH001 in combination with envafolimab and doxorubicin in patients with soft tissue sarcoma, which we expect in the second half of 2023

Fourth Quarter 2022 Financial Results

Cash and cash equivalents were $17.4 million at December 31, 2022, compared to $24.1 million at December 31, 2021, and is expected to fund the company into mid-2023

Research and development expenses for the fourth quarter of 2022 were $3.9 million, compared to $3.1 million for the fourth quarter of 2021

General and administrative expenses for the fourth quarter of 2022 were $2.0 million, compared to $4.6 million for the fourth quarter of 2021. The decrease was primarily attributable to legal expenses incurred in the fourth quarter of 2021 in connection with the arbitration with I-Mab

Net loss for the fourth quarter of 2022 was $7.0 million, compared to $7.7 million for the fourth quarter of 2021

Conference Call Details

To access the call by phone, please register using this link and you will be provided with dial-in details

A live webcast of the conference call will be available online from the Investor/Events and Presentation page of the Company’s website at www.traconpharma.com

After the live webcast, a replay will remain available on TRACON’s website for 60 days

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the pivotal ENVASARC Phase 2 trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients as well as multiple Phase 1 and Phase 2 clinical trials in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines. TRACON has received orphan drug designation from the U.S. Food and Drug Administration for envafolimab for patients with soft tissue sarcoma and fast track designation from the U.S. Food and Drug Administration for envafolimab for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy

About ENVASARC (NCT04480502

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. TRACON expects the trial to enroll more than 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into a cohort of treatment with single agent envafolimab at 600 mg every three weeks and 80 patients enrolled into a cohort of treatment with envafolimab at 600 mg every three weeks with Yervoy. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint

About YH001

YH001 is an IgG1 antibody against CTLA-4 that has shown enhanced antibody dependent cellular cytotoxicity and complement dependent cytotoxicity in vitro. In preclinical studies YH001 demonstrated superior T cell activation and superior tumor growth inhibition activity compared to ipilimumab. YH001 also demonstrated superior activity compared to ipilimumab in human transgenic mouse tumor models when combined with a PD-(L)1 antibody. In these models, single agent YH001 depleted regulatory T cells and increased CD8+ T cells in tumor tissue. YH001 is being studied with envafolimab and doxorubicin in a Phase 1/2 clinical trial sponsored by TRACON (NCT05448820), and has been studied in multiple Phase 1 trials in China and Australia sponsored by TRACON’s corporate partner Eucure, a division of Biocytogen

About TRC102

TRC102 (methoxyamine) is a novel small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA) and has orphan drug designation from the FDA in malignant glioma, including glioblastoma

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate to adenosine, which is highly immunosuppressive. TJ004309 was studied in a Phase 1 trial sponsored by TRACON (NCT03835949) to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.