On April 18, 2021 Transcenta Holding Limited (Transcenta), a clinical stage global biotherapeutics company with fully-integrated capabilities in discovery, development and manufacturing of antibody-based therapeutics, reported the first patient has been successfully dosed in Phase I clinical study of TST001, a humanized monoclonal antibody targeting human Claudin18.2 (CLDN18.2), in combination with CAPOX for the treatment of patients with first-line locally advanced unresectable or metastatic gastric cancer (Press release, Transcenta, APR 18, 2021, View Source [SID1234578147]).

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TST001 is a second-generation recombinant humanized monoclonal antibody targeted CLDN18.2，generated by Transcenta’s independently-developed Immune Tolerance Breaking Technology (IMTB) platform. TST001 can target and kill tumor cells expressing CLDN18.2 by leveraging mechanisms such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) through combining CLDN18.2 with high specificity and affinity. With advanced technology, the fucose content of TST001 was significantly reduced during the production, which further enhancing the ADCC-mediated tumor killing activity of TST001. TST001 demonstrated better antitumor efficacy than IMAB362 analogues in pharmacodynamic experiments in mice (in vivo). TST001 has been launched in clinical research in China and US in July 2020 (NCT04396821, NCT04495296/CTR20201281).

"CLDN18.2 is found to be overexpressed in many tumors including gastric cancer，pancreatic cancer and esophageal cancer. At present, the first-in-class drug IMAB362 has shown promising efficacy in phase II FAST study mainly in first-line gastric cancer patients with high CLDN18.2 expression. "Professor Lin Shen from Beijing Cancer Hospital, believes that "Rapidly advancing the study of the combination of TST001 and standard chemotherapy in first-line gastric cancer patients could help us to accelerate the assessment of its therapeutic value in large number of gastric cancer patients expressing CLDN18.2."

"Gastric cancer is the most common tumor species in China and Asia. About 70% of gastric cancer patients express CLDN18.2. TST001 is a second-generation recombinant humanized monoclonal antibody targeted CLDN18.2. Preclinical studies have found that TST001 can not only efficiently kill gastric cancer cells with high expression of CLDN18.2, but also be very effective against gastric cancer cells with moderate to high expression of CLDN18.2. TST001 has been launched in clinical research in China and US in July 2020. We hope to explore the safe tolerance and anti-tumor activity of TST001 combined with CAPOX in first-line gastric cancer patients through this study, so as to provide a basis for later registrational clinical studies." said Dr. Michael Shi, EVP, Head of Global R&D and CMO of Transcenta.

On April 18, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported the initiation of a Phase 2 study of the company’s lead drug candidate, STP705, for Keloid scar prevention (Press release, Sirnaomics, APR 18, 2021, View Source [SID1234578167]). The Phase 2, multi-center, randomized, double-blind, multiple-arm, controlled study is designed to evaluate the safety and efficacy of various doses of STP705 in reducing post-keloidectomy keloid recurrence.

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The primary endpoint of this trial is to measure the rate of recurrence in patients who have undergone surgery alone (receiving placebo) versus surgery and STP705 at three months, six months, and 12 months post-surgical excision.

"We anticipate that this important study should render additional data on STP705’s unique mechanism of action on skin fibrotic scarring, following the promising results in previous studies," said Patrick Lu, Ph.D., founder, President and CEO of Sirnaomics. "This approach for Keloid scar prevention is indicative of our strategy to leverage STP705’s dual-targeted inhibitory property and polypeptide nanoparticle-enhanced delivery to develop improved options for treating different cancer indications."

"Keloid scarring is a serious medical condition resulting in abnormal scar formation and pain along with having a very negative psychological impact on patients who suffer from the disease," said Michael Molyneaux M.D., Chief Medical Officer. "There is currently no treatment apart from surgical removal and this carries a very high recurrence rate. We seek to offer patients a viable alternative to prevent recurrence after surgical resection."

Sirnaomics expects to report initial clinical data from the Phase 2 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04844840.

About Keloid Scar
Keloids form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient’s quality of life, both physically and psychologically. Multiple studies on keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction.

Pathophysiology of keloids entails a prolonged inflammatory and proliferative phase of wound healing after injury. Among various cytokines promoting keloids formation, TGF-β1 is known as a key regulator of the aberrant fibrogenic response, while COX-2 acts a potent proinflammatory and proliferative mediator. When STP705 was locally injected into the human hypertrophic scar tissues, which were surgically removed from patients and implanted onto nude mice, the company observed scar size reductions, accompanying with not only target gene silencing but down regulation of fibrogenic markers including α-SMA, hydroxyproline, Collagen 1, and Collagen 3. Further analysis revealed that STP705 is able to induce fibroblast apoptosis both in vitro and in vivo. Therefore, the synergistic effect of simultaneous silencing of TGF-β1 and COX-2 may reverse skin fibrotic scarring through minimizing inflammation and activating fibroblast apoptosis. This mechanism of action of STP705 can be widely applied for treatment of many fibrotic conditions.

About STP705
Sirnaomics’ leading product candidate, STP705, is a siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression. The product candidate has received multiple IND approvals from both the US FDA and Chinese NMPA, including treatments of cholangiocarcinoma, nonmelanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma and primary sclerosing cholangitis. A Phase 2a study of STP705 for treatment of squamous cell skin cancer (isSCC) in adult patients demonstrated positive efficacy and safety results, with 76% of all patients (19/25) achieving complete histologically clearance and the two optimal dosing ranges achieving 90% histological clearance of tumor cell in the lesion. No significant or serious adverse events, including no significant cutaneous skin reactions, were reported in the study, and the company was able to define a clear therapeutic window in advance of later stage studies.

On April 16, 2021 Peptron, Inc. ("Peptron", KOSDAQ: 087010), a South Korea-based biotech company, and Qilu Pharmaceutical ("Qilu"), a leading vertically integrated pharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative medicines reported that the companies have entered into an exclusive licensing agreement for the manufacturing, development and commercialization of Peptron’s PAb001-ADC, the antibody-drug conjugate (the "ADC") product containing the anti-MUC1 monoclonal antibody PAb001 as effective of March 26, 2021 (Press release, Qilu Pharmaceutical, APR 16, 2021, View Source [SID1234578131]).

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Under the terms of the agreement, Peptron grants Qilu an exclusive global right and license to develop, manufacture, sell, and commercialize PAb001-ADC for the treatment of cancers.

PAb001-ADC is a pre-clinical ADC entering into Investigational New Drug ("IND") enabling studies. It targets MUC1, a high-potential ADC target for multiple solid and hematological malignancies. MUC1 is overexpressed in many cancers and is recognized as a promising molecular target for therapeutic development for various types of cancers.

"We are excited to collaborate with Qilu to achieve the global opportunity of this potentially differentiated PAb001-ADC developed by us," said Ho-il Choi, CEO of Peptron. "Qilu is one of the leading pharmaceutical companies with global expertise and capacity in innovative R&D, manufacturing and marketing in China."

"We are very pleased to establish the partnership with Peptron to obtain global rights to the asset with highly differentiated attributes," said Dr. Binhui (Ben) Ni, Chief Investment Officer and Chief Business Officer, Corporate Vice President of Qilu Pharmaceutical, "We look forward to working closely with Peptron and The National Medical Products Administration (NMPA) to bring it to the patients."

On April 16, 2021 Amgen (NASDAQ:AMGN) reported that it has successfully completed its previously announced tender offer to purchase all outstanding shares of common stock of Five Prime Therapeutics (NASDAQ:FPRX), a clinical-stage biotechnology company focused on developing immuno-oncology and targeted cancer therapies, for $38.00 per share in cash (Press release, Amgen, APR 16, 2021, View Source [SID1234578114]). The aggregate consideration to be paid by Amgen to complete the tender offer and the subsequent merger is approximately $1.9 billion without giving effect to related transaction fees and expenses.

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"Five Prime fits squarely within Amgen’s leading oncology portfolio and includes bemarituzumab, a Phase 3 trial-ready, first-in-class program for gastric cancer, the third leading cause of cancer mortality worldwide," said Robert A. Bradway, chairman and chief executive officer at Amgen. "Working with the dedicated professionals joining us from Five Prime, we plan to quickly move bemarituzumab into a Phase 3 study, bringing it one step closer to helping patients suffering from gastric cancer."

Amgen’s existing and complementary development capabilities in metastatic gastric and gastroesophageal junction cancers together with its biologics manufacturing expertise and global commercial footprint will help bemarituzumab reach patients in markets such as Japan, South Korea, and Latin America, where the prevalence of gastric cancer is high. Amgen will continue to review additional Five Prime oncology assets for the Amgen pipeline.

As of the expiration of the tender offer, approximately 40,392,569 shares were validly tendered and not properly withdrawn in the tender offer, representing approximately 87.8% of Five Prime’s outstanding shares, according to the depositary of the tender offer. The condition to the tender offer that at least one share more than 50% of Five Prime’s issued and outstanding shares be validly tendered and not properly withdrawn prior to the expiration of the tender offer has been satisfied. As a result, Amgen has accepted for payment all such validly tendered shares and will promptly (and in any event within two business days) pay for all such validly tendered shares.

Following the completion of the tender offer, Franklin Acquisition Sub, Inc., a wholly owned subsidiary of Amgen, merged with and into Five Prime, with Five Prime surviving the merger. As a result of the merger effected today, all remaining eligible Five Prime shares have been converted into the right to receive $38.00 per share in cash, minus any applicable withholding taxes and without interest, the same price that was paid in the tender offer (eligible shares exclude those for which holders properly demanded and perfected appraisal rights under Delaware law and those held by Amgen or its wholly owned subsidiaries or Five Prime). Following completion of the merger, Five Prime shares have ceased trading on the NASDAQ Global Select Market.

On April 16, 2021 IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a synthetic lethality-focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported clinical data from the ongoing Phase 1/2 trial evaluating darovasertib (IDE196) monotherapy and binimetinib combination therapy in patients with solid tumors, including Metastatic Uveal Melanoma (MUM) and Skin Melanoma (ClinicalTrials.gov Identifier: NCT03947385) (Press release, Ideaya Biosciences, APR 16, 2021, View Source [SID1234578132]).

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"The darovasertib single-agent one-year survival data in MUM is encouraging and compares favorably to historical survival rates in this indication, where a therapy has yet to be approved," said Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN. "The early partial responses observed in the darovasertib and binimetinib combination in MUM are exciting where historical response rates have been from zero to low to mid-single-digit percent, and we look forward to seeing the data set mature," said Richard Carvajal, MD, Co-Leader, Precision Oncology and Systems Biology Program, Director of Experimental Therapeutics and Director of the Melanoma Service, Columbia University Irving Medical Center.

Darovasertib Monotherapy Clinical Efficacy in Solid Tumors
There have been 81 darovasertib monotherapy BID MUM and 7 Skin Melanoma patients enrolled across the IDEAYA and Novartis Phase 1/2 clinical trials at the time of data and analyses cutoff on April 13th, 2021, with an aggregate of 88 patients evaluable for safety and 81 evaluable for efficacy based on RECIST 1.1. Reported data is preliminary and based on an unlocked database. Evaluation and follow-up of the monotherapy arm of the clinical trial continues.

Darovasertib Monotherapy Preliminary Results Summary

57% 1-Year Overall Survival (OS) Rate was observed in predominantly second line, third line and heavily pre-treated (out to 7 and 8 lines of prior treatment) Metastatic Uveal Melanoma (MUM) patients with 95% CI (44%, 69%); Historical 1-Year OS Rate in similar MUM populations has been reported at 37% (Source: Rantala 2019, Immunocore March 2021 presentation, Synthetic Control Arm, 2+ L)
Median OS of 13.2 months was observed in predominanantly second line, third line and heavily pre-treated (out to 7 and 8 lines of prior treatment) MUM patients with 95% CI (10.7 months, Not Reached); Historical median OS in similar MUM populations has been reported at approximately 7 months (Source: Rantala 2019, Immunocore March 2021, Synthetic Control Arm, 2+ L)
61% (n=46) of MUM patients out of 75 evaluable had tumor reduction per RECIST 1.1. evaluation, including 15 patients (20%) with >30% target lesion reduction and one confirmed complete response. In the Skin Melanoma cohort, 80% (n=4) of evaluable patients (n=5) had tumor reduction per RECIST 1.1. evaluation, including one confirmed partial response
Darovasertib Monotherapy Clinical Safety
Overall safety profile of darovasertib monotherapy is consistent with prior reports (Ref. 2019 AACR (Free AACR Whitepaper)) and includes primarily common low grade but manageable GI toxicities and hypotension.

Preliminary Darovasertib and Binimetinib Combination Clinical Efficacy in MUM
The combination of darovasertib plus binimetinib is being evaluated pursuant to a clinical trial collaboration and drug supply agreement with Pfizer, which the companies have amended to support a target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm in MUM. At the time of the data and analyses cutoff on April 13th, 2021, twenty four MUM patients have enrolled in the darovasertib and binimetinib combination study, including 8 patients dosed in the Phase 1/2 dose expansion cohort of the combination study. Reported data is preliminary and based on an unlocked database. Enrollment in the darovasertib and binimetinib combination arm of the clinical trial is ongoing.

Darovasertib and Binimetinib Combination Therapy Preliminary Data Summary

2 partial responses observed out of nine MUM patients with at least 2 post-baseline scans (22%) by RECIST 1.1 guidelines, including 1 confirmed partial response and 1 unconfirmed partial response (-40.5%) awaiting a confirmatory scan
79% of evaluable MUM patients with at least 1 post-baseline scan show tumor reduction; follow-up for overall response is still immature
Combination doses for Phase 1/2 dose expansion have been selected based on anticipation of activity and overall tolerability in a larger treatment cohort
Treatment-related adverse events observed in the darovasertib and binimetinib combination arm in MUM primarily include: nausea, vomiting, diarrhea, rash, edema, AST/ALT increase and CK increase (>10%); and hypotension (<10%)
IDEAYA’s clinical development strategy in MUM is focused on darovasertib combinations, including with binimetinib, a MEK inhibitor, and in a separate clinical study with crizotinib, a cMET inhibitor, each pursuant to the clinical trial collaboration and drug supply agreement with Pfizer.

Darovasertib Investor Day Webcast
IDEAYA will host an investor webcast with a presentation at 8:00 a.m. ET today. A link to the webcast and a copy of the presentation is posted on the Investor Relations Events section of the Company’s website at View Source The update may also be accessed by dialing 1-866-248-8441 (domestic) or 1-720-452-9102 (international) five minutes prior to the start of the call and providing the passcode 2793795. An archived replay of the webcast will be accessible for 90 days following the event.

Meredith McKean, MD, MPH, Associate Director, Melanoma and Skin Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, Nashville, TN, and Richard Carvajal, MD, Co-Leader, Precision Oncology and Systems Biology Program, Director of Experimental Therapeutics and Director of the Melanoma Service, Columbia University Irving Medical Center, will participate in the webcast.