On January 28, 2025 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a global clinical-stage biopharmaceutical company developing innovative cancer therapies, reported that it has entered into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED Therapeutics Inc. ("SEED"), a biotechnology company focused on Targeted Protein Degradation (TPD) technology and a subsidiary of the Company, for gross proceeds of approximately $35.4 million (Press release, BeyondSpring Pharmaceuticals, JAN 28, 2025, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-35-4-million-sale-of-a-portion-of-equity-interest-in-seed-therapeutics-to-advance-lead-asset-plinabulin-to-anti-cancer-registrational-studies [SID1234649903]). Upon completion of the transactions, BeyondSpring, together with SEED Technology Limited, a majority-owned indirect subsidiary of the Company, is expected to retain approximately 14.4% of SEED’s outstanding shares.

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Strategic Background and Rationale

Since 2016, BeyondSpring has been at the forefront of TPD innovation, incubating its proprietary TPD technology internally and co-founding SEED with Eli Lilly and Company in 2020. Through this pioneering sponsorship, SEED has grown into a leader in TPD, a revolutionary drug discovery approach targeting previously undruggable proteins. SEED has developed a robust pipeline of therapies in oncology and neurodegeneration, leveraging its proprietary molecular glue-based platform. Research collaborations with Eli Lilly and Company, and Eisai Co. Ltd. ("Eisai") further validate its leadership in TPD.

The recent Series A-3 financing led by Eisai, at a pre-money valuation of $100 million, underscores SEED’s innovation and market potential. The transactions announced today will enable BeyondSpring to unlock value while retaining a meaningful ownership stake in SEED. The $35.4 million in proceeds will advance BeyondSpring’s late-stage clinical trials of its lead asset, Plinabulin, ensuring critical resources without diluting shareholder equity.

Plinabulin: A First-in-Class Agent with Broad Potential

Plinabulin is a first-in-class anti-cancer agent which has been used in over 700 cancer patients with good tolerability. It is a differentiated tubulin binder, which releases immune defense protein GEF-H1, leading to dendritic cell maturation that drives both direct anti-cancer activity and immune system activation1,2. It has demonstrated durable anti-cancer benefits across multiple clinical studies and addresses significant unmet medical needs in oncology:

DUBLIN-3 (103) Study (Sept. 2024): In a global phase 3 study (n=549)3, Plinabulin combined with docetaxel achieved significant overall survival benefit, and doubling 2-year and 3-year survival rate in second- and third-line non-small-cell lung cancer (NSCLC) with EGFR wild type, compared to docetaxel alone (Press Release Link).
303 Study (Nov. 2024): Plinabulin combined with pembrolizumab and docetaxel achieved an 89.3% disease control rate and a median progression-free survival (PFS) of 8.6 months in 30 NSCLC patients who progressed on immune checkpoint inhibitors (Press Release Link).
302 Study (Mar. 2024): Enrollment began for first-line extended-stage small cell lung cancer (ES-SCLC) patients treated with Plinabulin, etoposide, platinum therapy, and pembrolizumab (Press Release Link).
Dr. Trevor Feinstein, MD, a lead principal investigator of the DUBLIN-3 Study at Piedmont Cancer Center, Atlanta, highlighted the critical need addressed by Plinabulin:

"There is a poor prognosis for NSCLC patients without targetable alterations whose disease has progressed on platinum-based therapies and immune checkpoint inhibitors. Over 60% of patients progress on PD-1/PD-L1 inhibitors in NSCLC4. Unfortunately, multiple high-profile phase 3 studies failed to show overall survival benefit in this hard-to-treat population compared to standard of care docetaxel, a drug approved over 20 years ago. The data from the DUBLIN-3 Study demonstrates that the addition and proper sequencing of Plinabulin to docetaxel has a favorable benefit/risk ratio compared with docetaxel alone and may have broad utility. In addition, current ongoing 303 and 302 Studies are targeting additional severe unmet medical needs, which Plinabulin’s mechanism of action can help address."

"With this capital, BeyondSpring is strategically positioned to advance our 303 and 302 studies in Plinabulin combination with immune checkpoint inhibitors to registrational trials and explore business development partnerships to bring Plinabulin to cancer patients with limited treatment options," said Dr. Lan Huang, Co-Founder, Chairman, and CEO of BeyondSpring. "At the same time, retaining a substantial stake in SEED Therapeutics ensures that we remain part of its continued success in revolutionizing drug discovery."

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, 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 securities laws of any such state or jurisdiction.

On January 28, 2025 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the acceptance of two abstracts for presentation at the ASCO (Free ASCO Whitepaper) GU 2025 Conference on Clarity’s COBRA and CLARIFY trials and an abstract on the COBRA trial at the AUA Annual Meeting 2025 (Press release, Clarity Pharmaceuticals, JAN 28, 2025, View Source [SID1234649892]). These conferences are among the world’s most prestigious in oncology and urology, and the acceptance of these abstracts is testament to the strength of Clarity’s data and the exciting prospects for the diagnostic 64Cu-SAR-bisPSMA to change the paradigm in the diagnosis and treatment of cancer.

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The abstracts on Clarity’s COBRA trial showcase the improved efficacy of 64Cu-SAR-bisPSMA at detecting lesions compared to currently approved PSMA PET agents, and the potential for this product to become a best-in-class diagnostic. 64Cu-SAR-bisPSMA was able to identify lesions prior to detection by the standard-of-care (SOC) PSMA PET products, which are known to have low sensitivity.

In a subset of participants in the COBRA study who underwent follow-up SOC PSMA PET, 70% of participants had a positive scan on same-day imaging and 90% on next-day imaging using 64Cu-SAR-bisPSMA, compared to 60% of participants using SOC PSMA PET where only same-day imaging is possible. The number of lesions across all participants (average sum of lesions across all readers) identified by 64Cu-SAR-bisPSMA was also higher (26.3 lesions on same-day imaging, 52.6 on next-day imaging) than that detected by SOC PET agents (20 lesions). Results indicate that 64Cu-SAR-bisPSMA is able to identify lesions from 29 days to more than 6 months earlier than SOC PSMA agents. Across all participants in the study, histopathology confirmed the presence of prostate cancer in lesions identified by 64Cu-SAR-bisPSMA in up to 78% of cases in which biopsies were performed, which was considerably higher compared to less sensitive methods (e.g. SOC imaging) used to verify the 64Cu-SAR-bisPSMA PET findings. With regards to the biopsies, 100% of lesions which were located outside of the prostate bed were determined as positive, with only 2 participants showing negative results. These 2 participants had lesions located in the prostate bed and had undergone the complete removal of their prostate as part of their initial treatment. The prostate bed is an area notoriously difficult to biopsy following surgery due to anatomical changes and scarring of surrounding tissues as a result of the procedure, which may lead to negative results despite the presence of cancer. Investigators stated that they would change their intended treatment plan in approximately half (48%) of their patients due to the findings of the 64Cu-SAR-bisPSMA PET.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "Our lead product, SAR-bisPSMA, continues generating impressive results as we work with world-class experts to conduct clinical research at the highest standard, bringing us closer to improving the diagnostic paradigm for prostate cancer patients around the world. It is a huge testament to the quality and importance of our data that it continues to be accepted for presentation at some of the world’s most prominent conferences.

"64Cu-SAR-bisPSMA has shown an impeccable safety profile and impressive diagnostic performance to date compared to current SOC PSMA PET agents, which are known to have significant sensitivity limitations. Not only is our product more effective on same-day imaging due to its dual-targeting "bis" structure, but the unique property of next-day imaging, enabled by the longer half-life of copper-64 isotopes, also opens a myriad of opportunities for significantly improving the accuracy of cancer diagnosis and making more informed treatment decisions for men with prostate cancer.

"The results presented in the most recent COBRA abstracts highlight how 64Cu-SAR-bisPSMA could change the scene of prostate cancer diagnostics. With 90% of next-day scans identifying prostate cancer, in comparison to only 60% on SOC PSMA PET scans, and identifying over 2.6 times the number of lesions with 64Cu-SAR-bisPSMA over the approved diagnostics, 64Cu-SAR-bisPSMA could be the game changer. The data provides physicians crucial information to make more informed decisions about treatment, and the high response from investigators in the COBRA trial who intended to change their treatment plan is an indication of how far reaching these changes could be. This opens the door for patients to potentially receive better treatment for their cancer based on these findings, improving their outcomes and quality of their lives.

"The data from the COBRA study, as well as from our earlier PROPELLER trial in the pre-prostatectomy setting, were used to support the design of our second registrational trial with 64Cu-SAR-bisPSMA, AMPLIFY, in patients with biochemical recurrence (BCR) of prostate cancer, planned to commence in the coming months. This trial, in conjunction with the ongoing pivotal CLARIFY trial, which currently has over 20 sites actively recruiting in the U.S. and Australia, is intended to provide evidence to support the U.S. Food and Drug Administration (FDA) approval of 64Cu-SAR-bisPSMA as a novel diagnostic imaging agent for newly diagnosed prostate cancer patients as well as those in BCR of their disease, bringing us closer to achieving our ultimate goal of improving treatment outcomes for people with cancer."

Title Conference and Session details
COBRA: Assessment of the efficacy of 64Cu-SAR-bisPSMA using histopathology as reference standard in patients with biochemical recurrence of prostate cancer following definitive therapy ASCO GU
Date: Thursday, February 13, 2025

Time: 11:25 AM – 12:45 PM PT; 5:45 PM – 6:45 PM PT

Session Title: Trials in Progress Poster Session A: Prostate Cancer

Abstract #: 44

Poster Bd #: A22

CLARIFY: Positron emission tomography using 64Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy — A phase 3 diagnostic performance study ASCO GU
Date: Thursday, February 13, 2025

Time: 11:25 AM – 12:45 PM PT; 5:45 PM – 6:45 PM PT

Session Title: Trials in Progress Poster Session A: Prostate Cancer

Abstract #: TPS429

Poster Bd #: M27

COBRA: Assessment of 64Cu-SAR-bisPSMA and standard of care prostate-specific membrane antigen Positron Emission Tomography in patients with biochemical recurrence of prostate cancer following definitive therapy AUA
Date: Sunday, April 27, 2025

Time: 9:30 AM – 11:30 AM PT

Session Title: MP13: Prostate Cancer: Staging

Room: To be announced

Presentations will be available on Clarity’s website after the conferences: claritypharmaceuticals.com/pipeline/scientific_presentations

About SAR-bisPSMA
SAR-bisPSMA derives its name from the word "bis", which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu-SAR-bisPSMA is an unregistered product. The safety and efficacy of 64Cu-SAR-bisPSMA has not been assessed by health authorities such as the U.S. FDA or the Therapeutic Goods Administration (TGA). There is no guarantee that this product will become commercially available. Among 82 patients who received 64Cu-SAR-bisPSMA in PROPELLER and COBRA, 2 adverse reactions were reported in 2 participants (mild occasional metallic taste and moderate worsening of type II diabetes, both resolved).

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death in men worldwide3. Prostate cancer is the second-leading cause of cancer death in American men. The American Cancer Institute estimates in 2025 there will be about 313,780 new cases of prostate cancer in the U.S. and around 35,770 deaths from the disease.

On January 27, 2025 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported positive topline results from the overall survival (OS) analysis of the Phase III INAVO120 study investigating ItovebiTM (inavolisib) in combination with palbociclib (Ibrance) and fulvestrant for people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer (Press release, Genentech, JAN 27, 2025, View Source [SID1234649900]). The study met its key secondary endpoint, showing a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen compared with palbociclib and fulvestrant alone.

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"The INAVO120 overall survival results show that the Itovebi-based regimen not only delayed disease progression, but also helped people with advanced HR-positive, PIK3CA-mutated breast cancer live longer," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "These findings underscore our ambition to improve survival rates for people with breast cancer. The Itovebi-based regimen has the potential to become the new standard of care for these patients."

These OS results build upon the previously reported primary analysis, which showed that the Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.001) in the first-line setting. OS data were immature at the time of primary analysis, but a clear positive trend was observed at that time (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 [boundary of 0.0098]). No new safety signals were observed since the previous analysis. The full results from the OS analysis will be presented at an upcoming medical meeting.

The U.S. Food and Drug Administration (FDA) approved the Itovebi-based regimen in October 2024 for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Data from INAVO120, recently published in the New England Journal of Medicine, are also being reviewed by other global health authorities, including the European Medicines Agency.

Itovebi is currently being investigated in four company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122, INAVO123) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. We are exploring additional studies in breast cancer and other tumor types with the hope of bringing the benefit of this targeted therapy to more people with PIK3CA-mutated cancer and addressing patient unmet needs.

About the INAVO120 study

INAVO120 study [NCT04191499] is a Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of ItovebiTM (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations:

in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 inhibitor and endocrine combination therapy (INAVO121; NCT05646862).
in combination with dual HER2 blockade versus dual HER2 blockade and optional physician’s choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
in combination with CDK4/6i and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in endocrine-sensitive, PIK3CA-mutated HR-positive/HER2-negative breast cancer (INAVO123; NCT06790693).

About hormone receptor (HR)-positive breast cancer
HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.

What is Itovebi?

Itovebi (inavolisib) is a prescription medicine used in combination with the medicines palbociclib and fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) gene, and has spread to nearby tissue or lymph nodes (locally advanced), or to other parts of the body (metastatic), and has come back after hormone (endocrine) therapy.

Your healthcare provider will test your cancer for abnormal PIK3CA genes to make sure that Itovebi is right for you.

It is not known if Itovebi is safe and effective in children.

Important Safety Information

What are the possible side effects of Itovebi?

Itovebi may cause serious side effects, including:

High blood sugar levels (hyperglycemia). High blood sugar is common with Itovebi and may be severe. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with Itovebi. Your blood sugar levels may be monitored more often if you have a history of Type 2 diabetes. Your healthcare provider may also ask you to self-monitor and report your blood sugar levels at home. This will be required more frequently in the first 4 weeks of treatment. If you are not sure how to test your blood sugar levels, talk to your healthcare provider. You should stay well-hydrated during treatment with Itovebi. Tell your healthcare provider right away if you develop symptoms of high blood sugar, including:
difficulty breathing
nausea and vomiting (lasting more than 2 hours)
stomach pain
excessive thirst
dry mouth
more frequent urination than usual or a higher amount of urine than normal
blurred vision
unusually increased appetite
weight loss
fruity-smelling breath
flushed face and dry skin
feeling unusually sleepy or tired
confusion
Mouth sores (stomatitis). Mouth sores are common with Itovebi and may be severe. Tell your healthcare provider if you develop any of the following in your mouth:
pain
swelling
redness
ulcers
Diarrhea is common with Itovebi and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney injury. Tell your healthcare provider right away if you develop diarrhea, stomach-area (abdominal pain), or see mucus or blood in your stool during treatment with Itovebi. Your healthcare provider may tell you to drink more fluids or take medicines to treat your diarrhea.
Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with Itovebi if you develop certain serious side effects.

The most common side effects and abnormal blood test results of Itovebi when used in combination with palbociclib and fulvestrant include:

decreased white blood cell counts, red blood cell counts, and platelet counts
decreased blood levels of calcium, potassium, sodium, and magnesium
increased creatinine blood levels
tiredness
increased blood levels of the liver enzyme alanine transaminase (ALT)
nausea
rash
loss of appetite
COVID-19 infection
headache
Itovebi may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.

These are not all the possible side effects of Itovebi. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or View Source You may also report side effects to Genentech at (877) 436-3683.

Before you take Itovebi, tell your healthcare provider about all of your medical conditions, including if you:

have a history of diabetes or high blood sugar
have kidney problems
are pregnant or plan to become pregnant. Itovebi can harm your unborn baby.

Females who are able to become pregnant:

Your healthcare provider will check to see if you are pregnant before you start treatment with Itovebi.
You should use effective non-hormonal birth control (contraception) during treatment and for 1 week after your last dose of Itovebi. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Itovebi.

Males with female partners who are able to become pregnant:

You should use effective birth control (contraception) during treatment with Itovebi and for 1 week after your last dose.
are breastfeeding or plan to breastfeed. It is not known if Itovebi passes into your breastmilk. Do not breastfeed during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with Itovebi.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On January 27, 2025 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a life sciences company developing novel targeted oncology therapies and commercializing RenovoCath, a novel, FDA-cleared delivery platform, reported an abstract presentation highlighting promising pharmacokinetic (known as PK) data from the use of RenovoRx’s patented Trans-Arterial Micro-Perfusion (TAMP) therapy platform in treating locally advanced pancreatic cancer (LAPC) (Press release, Renovorx, JAN 27, 2025, View Source [SID1234649899]).

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The abstract was presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) 2025, by Paula Novelli, MD, University of Pittsburgh Medical Center, which is currently underway in San Francisco, CA.

Dr. Novelli, together with her co-authors, presented "Intra-arterial Gemcitabine Versus Intravenous Gemcitabine: Pharmacokinetic Sub-study of the TIGeR-PaC Phase 3 Clinical Trial," a sub-study of RenovoRx’s ongoing pivotal Phase III TIGeR-PaC clinical trial in LAPC. In this sub-study, PK analyses were performed on a sample of participants across TIGeR-PaC study clinical sites. These analyses compared treatment with intra-arterial gemcitabine (IAG), using the RenovoCath delivery system via TAMP, versus systemic intravenous gemcitabine, which is the current standard of care for patients with LAPC.

Results of the sub-study showed RenovoRx’s IAG approach to drug delivery via TAMP decreased systemic levels of gemcitabine versus standard of care. In addition to providing increased local drug potency, the IAG approach may also be beneficial to decreasing gemcitabine-related systemic side effects. TAMP is designed to ensure precise therapeutic delivery across the arterial wall near the tumor site to bathe the target tumor, while potentially minimizing a therapy’s toxicities versus systemic intravenous therapy.

"Pancreatic cancer remains one of the most challenging cancers to treat, and this new data further highlights the potential of RenovoRx’s TAMP therapy platform as a transformative therapeutic option," said Paula Novelli MD, TIGeR-PaC Principal Investigator at University of Pittsburgh Medical Center. "TAMP is intended to direct a drug and more effectively target the tumor while minimizing systemic impact, and this sub-study shows that despite delivering more gemcitabine in a shorter time, the total systemic drug exposure was significantly lower compared to intravenous treatment. This data further demonstrates that TAMP has the potential to deliver gemcitabine to the tumor more efficiently, enhancing local treatment effectiveness while reducing the broader impact on the body, ultimately minimizing the systemic side effects of chemotherapy."

About the TIGeR-PaC Clinical Trial

TIGeR-PaC is an ongoing Phase III randomized multi-center study evaluating the proprietary TAMP (Trans-Arterial Micro-Perfusion) therapy platform for the treatment of locally advanced pancreatic cancer (LAPC.) RenovoRx’s first product candidate using the TAMP technology, is a novel investigational oncology drug-device combination utilizing RenovoRx’s FDA-cleared RenovoCath device for the intra-arterial administration of chemotherapy, gemcitabine.

The first interim analysis in the Phase III clinical trial was completed in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The study’s primary endpoint is an Overall Survival benefit with secondary endpoints including reduced side effects versus standard of care. The second interim analysis for this study will be triggered by the 52nd event (i.e., patient death), which is estimated to occur in early 2025. The second interim data readout is anticipated to occur by the end of the first half of 2025, with the timing for such readout, however, being dependent on customary factors such as time needed for analysis. RenovoRx is also aiming to complete patient enrollment in the TIGeR-PaC study in the first half of 2025.

About RenovoCath

Based on its FDA clearance, RenovoCath is intended for the isolation of blood flow and delivery of fluids, including diagnostic and/or therapeutic agents, to selected sites in the peripheral vascular system. RenovoCath is also indicated for temporary vessel occlusion in applications including arteriography, preoperative occlusion, and chemotherapeutic drug infusion. For further information regarding our RenovoCath Instructions for Use ("IFU"), please see: IFU-10004-Rev.-F-Universal-IFU.pdf.

On January 27, 2025 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that it presented Phase 1 safety and biomarker data on ST316, a novel peptide antagonist of β-catenin, during a poster session at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium (Press release, Sapience Therapeutics, JAN 27, 2025, View Source [SID1234649898]).

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ST316 is a first-in-class antagonist of β-catenin and its co-activator, BCL9, that is designed to selectively shut down the Wnt/β-catenin signaling pathway. The Phase 1 Dose Escalation study enrolled patients with advanced solid tumors likely to harbor abnormalities in the Wnt/β-catenin pathway to assess the safety, pharmacokinetics (PK), biomarker and preliminary activity of ST316, and to recommend a Phase 2 dose.

"With signals of anti-tumor activity, strong pharmacodynamic data, and a clean safety profile, we are pleased that the ST316 Phase 1 Dose Escalation study demonstrated clinical proof-of-concept as a single agent, in a patient population in which single agent response is limited," commented Dr. Abi Vainstein-Haras, Sapience’s Chief Medical Officer. "ST316’s tolerability as a single agent, together with the biomarker data from its Phase 1 study, are encouraging for its continued development in our ongoing Phase 2 Dose Expansion study, which is evaluating ST316 across multiple combinations and lines of treatment in colorectal cancer (CRC)."

Summary of Phase 1 Dose Escalation Results:

ST316 disrupts the interaction of β-catenin with BCL9 to result in Wnt/β-catenin pathway inhibition.
ST316 was shown to be safe and well tolerated at all doses tested.
The prolonged stable disease noted with single agent ST316 is consistent with early signals of anti-tumor activity.
ST316 demonstrates tumor uptake and target engagement, as shown by a shift in the localization of β-catenin from nucleus to cytoplasm/membrane following treatment in 4 of 7 patients assessed.
ST316 significantly reduced the expression of immunosuppressive polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in all Phase I patients that displayed elevated baseline levels (n=7).
Based on the safety and pharmacodynamic effects that are consistent with the mechanism of action, ST316 is now being tested in combination with chemotherapy in advanced colorectal cancer patients across different lines of treatment.
Poster Presentation:

Title: "Safety and biomarker assessment of ST316, a novel peptide antagonist of ß-catenin, in patients with advanced solid tumors"
Session: Poster Session C: Cancers of the Colon, Rectum and Anus
Date/Time: Saturday, January 25, 2025, 7:00 am to 7:55 am PST
Abstract Number: 286
Presenting Author: Anthony El-Khoueiry, MD

More information can be found on the ASCO (Free ASCO Whitepaper) GI website.

About ST316
ST316 is a first-in-class antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression and immune exclusion in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 exposure in cancer cells prevents BCL9-driven nuclear localization of β-catenin and inhibits formation of the Wnt enhanceosome protein complex. Disruption of this interaction selectively suppresses the transcription of oncogenic Wnt target genes that regulate proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes that regulate the immunosuppression of the tumor microenvironment. ST316 creates a pro-immune tumor microenvironment and in preclinical models has shown to be synergistic with checkpoint inhibition. Due to its selectivity and downstream modulation of the Wnt/β-catenin pathway, ST316 presents an opportunity to safely and effectively target Wnt/β-catenin driven pathologies without the toxicities previously seen with other Wnt pathway agents.

ST316-101 (NCT05848739) is a first-in-human, open-label, Phase 1-2 Dose Escalation and Expansion study designed to determine the safety, tolerability, PK, PD and early efficacy of ST316. The Phase 1 Dose Escalation portion of the study tested various dose levels of ST316 in patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including CRC. ST316 is currently being tested in the Phase 2 portion of the study in CRC patients in combination with relevant standards of care and in multiple lines of treatment. The U.S. FDA has granted Orphan Drug Designation to ST316 for the treatment of familial adenomatous polyposis (FAP).