On April 17, 2023 Sporos BioDiscovery, Inc. (a wholly owned affiliate of Sporos Bioventures, "Sporos" or the "Company"), a precision oncology company developing a diversified pipeline of small molecule therapeutic candidates, reported preclinical data for its lead candidate, SPR1-0117, a next-generation TEAD inhibitor at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, FL (Press release, Sporos Bioventures, APR 17, 2023, View Source [SID1234630175]).

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SPR1-0117 targets cancers driven by mutations in the Hippo pathway, a key regulator of cell proliferation and oncogenesis not yet extensively targeted in precision oncology. The YAP1/TAZ co-activators and the TEAD family of transcription factors, which consists of four paralogs (TEAD1-4), execute the pro-cancerous effects of the Hippo pathway through transcription of pro-proliferative and anti-apoptotic genes. Hippo pathway activation has also emerged as a key mechanism of resistance to inhibitors of the MAPK pathway, making TEAD inhibitors a prime candidate for combination therapy with therapeutics targeting the MAPK pathway.

Sporos BioDiscovery’s bioinformatic analyses identified that selective inhibition of both TEAD1 and TEAD4 drives improved biological impact as compared to TEAD1 inhibitors alone, while inhibition of TEAD2 and TEAD3 were observed as undesirable due to the potential for paradoxical adverse stimulation of cell proliferation and kidney toxicity, respectively.

"We are excited to share this new data demonstrating the deep and broad biological activity of SPR1-0117 both in vitro and in vivo, not only in benchmark models of cancers driven by Hippo-pathway mutations but in a number of cell lines beyond that of mesothelioma and NF2 mutations, including in cell lines showing only a nuclear YAP/TAZ hyperactivity. We believe this broad activity is driven by SPR1-0117’s isoform selectivity profile which inhibits both TEAD1 / TEAD4. We believe this profile may unlock the potential of SPR1-0117 as a monotherapy in a wide array of tumors with Hippo driver mutations compared to inhibitors binding primarily TEAD1," said Stephen Rubino, Ph.D., Chief Executive Officer of Sporos Bioventures.

Dr. Rubino continued "We also see greater depth of biological response in benchmark models, with close to 80% frank regression in large, established tumors, a feat unaccomplished by other TEAD inhibitors to date. Overall, we believe SPR1-0117’s TEAD1 / TEAD4 isoform selectivity profile has been optimized as a potential best-in-class TEAD inhibitor for both monotherapy and in combination with MAPK and RTK inhibitors. We are on track to initiate IND-enabling studies for our TEAD inhibitor program this quarter and look forward to advancing our lead candidate into the clinic in 2024."

Data reported in the poster presentation from AACR (Free AACR Whitepaper) demonstrated SPR1-0117 has showed strong monotherapy activity across multiple in vitro models, including several non-mesothelioma cell lines. In addition, SPR1-0117 shows low nM potency and strong single-agent activity against TEAD-dependent benchmark in vivo models, including H226 NF2-null mesothelioma, as well as in vivo efficacy beyond mesothelioma in SCC25, an oral squamous cell carcinoma. SPR1-0117 has also demonstrated a promising ADME and safety profile in preclinical models and was shown to be well tolerated, including no significant findings of kidney toxicity, in a seven-day repeat dosing study in rats at greater than 10-times the drug exposure required for efficacy in mice.

The published poster is now available in the News & Events section of the Sporos Bioventures website.

On April 17, 2023 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported that the company will host a webcast to share data from its SB101 clinical study with SON-1010 in oncology patients (NCT05352750) on Tuesday, April 18, 2023 at 5:00 pm ET (Press release, Sonnet BioTherapeutics, APR 17, 2023, View Source [SID1234630173]).

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Webcast presenters will include:

Richard Kenney, M.D., Chief Medical Officer
Pankaj Mohan, Ph.D., Sonnet Founder and Chief Executive Office

The webcast at 5:00 pm ET, with an accompanying presentation, will be accessible under News & Events, IR Calendar in the Investors section of the company’s website. The archived audio webcast will be available on Sonnet’s website following the call.

To participate in the webcast, please see the following details:

Webcast Link: View Source;tp_key=f6d5c78778
Toll Free: 1-877-869-3847
International: 201-689-8261
Conference ID: 13737737
AACR Poster Presentation Details:

Title: Clinical development of a novel form of interleukin-12 with extended pharmacokinetics
Session Title: Phase I and First-in-Human Clinical Trials in Progress
Presentation Type: Poster
Session Date and Time: Tuesday April 18, 2023, 1:30 pm – 5:00 pm ET
Abstract Number: CT245
Location: Poster Section 46

On April 17, 2023 Pieris Pharmaceuticals, Inc. (Nasdaq:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, reported the presentation of cinrebafusp alfa (PRS-343) clinical results from the Company’s study in 2L+ HER2-positive gastric cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting being held in Orlando, Florida on April 14-19, 2023 (Press release, Pieris Pharmaceuticals, APR 17, 2023, View Source [SID1234630172]). The study’s principal investigator, Dr. Geoffrey Ku, will present these encouraging results at 1:30 PM EDT on April 17, 2023, which include an unconfirmed 100% objective response rate and promising emerging durability profile in the five patients enrolled into the study before discontinuation of enrollment for strategic reasons. A copy of the poster can be viewed here from 1:30 PM EDT today.

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"The power and potential of both cinrebafusp alfa and the 4-1BB franchise can be seen in this exciting signal," stated Shane Olwill, Chief Development Officer of Pieris. "The ability to drive response in patients who progressed on the most potent currently available therapies provides further evidence of the differentiation of cinrebafusp alfa in the HER2 landscape as well as the overall 4-1BB franchise. Beyond cinrebafusp alfa, we look forward to the progression of-and future data read-outs for-the broader 4-1BB franchise, including our PD-L1/4-1BB bispecific in collaboration with Servier in Phase 1 studies, our CD228/4-1BB bispecific with Seagen in Phase 1 studies, and our GPC-3/4-1BB bispecific with Boston Pharmaceuticals entering the clinic shortly."

The presented data from the multi-center, open-label Phase 2 clinical study evaluating a combination of cinrebafusp alfa, ramucirumab and paclitaxel in HER2-positive gastric cancer patients provide further encouraging evidence of clinical activity for this program. The combination regimen was well tolerated, and all patients experienced a partial clinical response, with three patients remaining on study as of the abstract submission cut-off date of December 19, 2022. Each patient received trastuzumab and a checkpoint blockade in prior lines of therapy, and three patients previously received-and progressed on-trastuzumab deruxtecan. Pieris is considering a range of transactions to facilitate the continuation of cinrebafusp alfa, from an immuno-oncology focused spinout to traditional partnering transactions, given the emerging transformative activity seen in gastric cancer and exciting potential in other HER2 settings.

About Cinrebafusp Alfa:

Cinrebafusp alfa, is a HER2/4-1BB bispecific designed for the treatment of HER2-expressing cancers. Previously reported Phase 1 study results provided initial evidence showing that cinrebafusp alfa was generally well-tolerated and resulted in durable responses-including complete response-in patients with HER2-positive malignancies.

On April 17, 2023 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, reported that in vivo data from a hepatocellular carcinoma model provides insight into the mechanism by which locally administered mouse-targeted PH-762 (mPH-762) exerts systemic anti-tumor efficacy ("abscopal effect") (Press release, Phio Pharmaceuticals, APR 17, 2023, View Source [SID1234630171]).

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In the study, intratumoral administration of mPH-762 stimulated a local anti-tumor immune response and generated systemic tumor-reactive memory T cells, suggesting that the abscopal effects of PH-762 are mediated by the immune system.

"These preclinical study results support intratumoral use of PH-762 in the clinical setting, with deeper understanding of the mechanism of abscopal efficacy," said Dr. Mary Spellman, Phio’s Acting Chief Medical Officer. "In addition, immune-related adverse events noted with systemic PD-1 inhibition may be mitigated by intratumoral administration."

PH-762 is under clinical development in a phase 1b trial for neoadjuvant treatment of advanced resectable melanoma.

Presentation Details:

Poster Title: Intratumoral PH-762, a self-delivering RNAi therapeutic (INTASYL) targeting mouse PD-1, generates systemic tumor-specific memory CD8 T cells, providing a mechanism for abscopal efficacy toward untreated tumors in a murine hepatocarcinoma model.

Session Date and Time: Monday, April 17, 2023 from 9:00 AM – 12:30 PM EST

On April 17, 2023 PharmaMar (MSE:PHM) reported four new abstracts from clinical trials of its compounds Zepzelca (lurbinectedin), ecubectedin (PM14) and PM534 at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), being held in Orlando, Florida (USA) from April 14-19 (Press release, PharmaMar, APR 17, 2023, View Source [SID1234630169]).

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Among the studies to be presented, the abstract entitled " Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SFLN11 are biomarkers for a better response", presents lurbinectedin activity results obtained in a panel of tumor cells that express the four transcription factors (ASCL1, NEUROD1, YAP1, POU2F3) which permit the molecular classification of SCLC. Moreover, in both in vitro and in vivo studies, as well as in biopsies obtained from patients, a possible predictive biomarker of response to lurbinectedin is identified, SLFN11.

Two abstracts will be presented at the congress on PharmaMar’s new marine-derived anti-tumor compound, PM534, which is obtained by chemical synthesis and is currently in Phase I clinical development. The first of the abstracts, entitled "PM534 is a novel microtubule-destabilizing agent with high affinity and potent antineoplastic properties", demonstrates by X-ray crystallography that PM534 binds to its target, tubulin, inducing a strong antitumor effect in vitro and in vivo. This research has been carried out in collaboration with CSIC (Spanish National Research Council) researchers. The second, entitled "The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vivo and in vitro", shows that, as a result of its high affinity for tubulin, it acts by destabilizing the microtubular network in the tumor cell, resulting in potent antitumor activity in vitro and in vivo. In addition, PM534 is a potent inhibitor of angiogenesis, which prevents the formation of blood vessels necessary for tumor growth.

Finally, PharmaMar will present the abstract "Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vivo and in vitro". This antitumor compound induces tumor cell death through apoptosis by inhibiting the activated transcription. This mechanism of action results in a very potent antitumor activity in vitro and in vivo models. Ecubectedin is currently in Phase II clinical development.

PharmaMar’s abstracts at AACR (Free AACR Whitepaper) 2023

PRODUCT TITLE LEAD AUTHOR ABSTRACT
Zepzelca (lurbinectedin) Lurbinectedin shows potent activity in all four molecular subtypes of small cell lung cancer (SCLC) and POU2F3 and SFLN11 are biomarkers for a better response Eva María Garrido-Martín, PhD ABSTRACT: 6247 POSTER SESION: Experimental and Molecular Therapeutics
PM534 PM534 is a novel microtubule-destabilizing agent with high affinity and potent antineoplastic properties Eva María Garrido-Martín, PhD ABSTRACT: 6239 POSTER SESION: Experimental and Molecular Therapeutics
PM534 The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vivo and in vitro Eva María Garrido-Martín, PhD ABSTRACT: 6243 POSTER SESION: Experimental and Molecular Therapeutics
Ecubectedin (PM14) Ecubectedin is a novel transcriptional inhibitor that displays potent antitumor effects in vivo and in vitro Eva María Garrido-Martín, PhD ABSTRACT: 1622 POSTER SESION: Experimental and Molecular Therapeutics