On December 14, 2022 Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), reported that a third patient has achieved a complete response (CR) among the first 24 patients (23 evaluable) enrolled in GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study (Press release, Geneos Therapeutics, DEC 14, 2022, View Source [SID1234625281]). Overall response rate by RECIST 1.1 is 30.4% in the evaluable patients consisting of three complete responses, four partial responses, six stable disease, and ten progressive disease.

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GT-30 is evaluating safety, immunogenicity, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first line tyrosine kinase inhibitors (sorafenib or lenvatinib). HCC is characterized by a low tumor mutational burden and is resistant to immune checkpoint monotherapy in the majority of patients due to the immune-excluded tumor microenvironment.

In addition to the three CRs, a fourth patient is also cancer-free after liver and lung lesions shrank to become fully responsive to surgery and radiation, thereby achieving secondary resectability.

Among all patients to date, there have been no vaccination-related serious adverse events (SAEs). Vaccination-related AEs, mostly injection site reactions, have been transient and mild and all Grades 1 and 2.

The Geneos PTCV approach is distinguished from other cancer vaccine platforms in offering a means to vaccinate virtually all patients with all of their neoantigens, and to do so rapidly. PTCVs are DNA-based rather than mRNA, viral vector, or peptide. Unlike these alternatives, Geneos DNA vaccines have the capacity to include up to 40 neoantigens in each vaccine, and up to 80 neoantigens merely by combining two DNA plasmids for each patient.

The most recent CR, a 72 year old male with stage IVa HCC whose PTCV included 40 neoantigens, highlights the value of vaccinating with as many neoantigens as possible. The patient developed therapeutically useful T cell responses to 38 of the 40 vaccine neoantigens, as confirmed by ELISpot analysis. In contrast to the large neoantigen capacity of Geneos’ PTCVs, a vaccine based on a platform with a limited neoantigen capacity would have had to compromise on the vaccine neoantigens delivered, thereby likely limiting efficacy.

"We were confident going into this study of the potential of Geneos PTCVs to offer a level of efficacy never seen previously with a cancer vaccine," stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. "This latest complete response confirms just how groundbreaking our approach is, not only among cancer vaccines but more broadly among oncology therapeutics. We know of no other cancer treatment which offers the potential for such profound efficacy, even in patients with advanced cancers, with the side effect profile, as seen to date, of a typical seasonal flu shot," added Dr. Sardesai.

GT-30 Trial of Geneos’ Personalized Therapeutic Cancer Vaccines
In the GT-30 trial, DNA plasmid-encoded personalized therapeutic cancer vaccine (PTCV) together with plasmid-encoded interleukin-12 (pIL12, a T cell-stimulating cytokine) adjuvant are administered via intradermal injection followed by electroporation (EP) in combination with pembrolizumab. The potential utility of this combination was suggested by preclinical studies which demonstrate Geneos’ PTCV to rescue PD-1 in murine tumor therapeutic challenge models. Geneos’ PTCVs have been engineered to drive a strong CD8+ T cell response against the tumor. CD8 cells are the killing machines of the immune system, seeking out and destroying cancer cells, but have been difficult to induce using prior vaccine approaches. Adjuvant pIL12 and EP serve to optimize the effectiveness of peripheral vaccination, and their utility is seen by the effective CD4+/CD8+ T cell responses observed to the delivered neoantigens in the GT-30 patients. Each patient’s PTCV is designed based on their unique tumor neoantigens (abnormal mutations and genomic variations produced by cancer cells), and unlike for other personalized platforms, in most every case, Geneos’ PTCVs include all of a patient’s specific neoantigens. This removes any requirement to try to pre-select the "high value" neoantigens accurately and, instead, leaves it to nature to decide which ones will matter for triggering the desired immune response. PTCV manufacturing "needle to needle" time, i.e. from biopsy to treatment, is six to eight weeks and is in process of being reduced to three to four weeks.

Based on the full 24-patient data, which were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting last month, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023. In parallel, the company is developing plans with its medical advisors for a potential registrational trial in advanced HCC and preparing for discussions with regulatory agencies.

On December 14, 2022 Sirnaomics Ltd. (the "Company" or "Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported the interim results of part-one of an ongoing Phase IIb clinical trial of STP705 for the treatment of Cutaneous Squamous Cell Carcinoma In Situ (isSCC) (Press release, Sirnaomics, DEC 14, 2022, View Source [SID1234625280]). The interim results showed that the majority (78%) of 32 patients with STP705 treatment achieved histological clearance. One of the three treatment cohorts achieved 89% histological clearance. STP705 is an siRNA (small interfering RNA) therapeutic that takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down bothTGF-β1 and COX-2 gene expression.

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The two-part, double-blind, randomized, placebo-controlled Phase IIb study is designed to evaluate the safety and efficacy of various doses of STP705, administered as an intralesional injection in subjects with isSCC. In the part-one of the study, we have treated 32 patients with 30 μg/ml, 60 μg/ml and 90 μg/ml of STP705, respectively, and 12 patients with 0 μg/ml placebo weekly. After six-week repeated dosing, we collected tissue samples from the treatment sites followed by histological analysis.

This interim report is specifically for part-one of the study results with a total of 44 patients. Based on our Phase IIb study plan, part-two of this study will include 60 additional subjects who will receive selected doses or placebo for a total of more than 100 subjects. Enrolled subjects will be randomly allocated to receive STP705 or placebo injection once a week for a total of six weeks. In the seventh week, the lesion will be excised.

"The positive clinical readouts of the part-one study of this Phase IIb trial provide a further validation of our STP705 for treatment of non-melanoma skin cancers." said Dr. Patrick Lu, Founder, Chairman of the Board, Executive Director, President and CEO of Sirnaomics. "With more clinical results from this study and the cutaneous Basal Cell Carcinoma (BCC) study (Sirnaomics News Release at PR Newswire, August 29, 2022), we feel more enthusiastic about this novel RNAi cancer therapeutics for treatment of Squamous Cell Carcinoma (SCC), addressing a broader unmet patient need."

"In our study thus far, patients who received various doses of STP705 over six weeks achieved better histological clearance of isSCC excised lesions than the patients who received a placebo," said Dr. Michael Molyneaux, M.D., Executive Director and Chief Medical Officer of Sirnaomics. "As we move into the latter phase of the clinical trial, we will use this information to determine which doses we deem most effective for treating SCC, which is a type of nonmelanoma skin cancer that affects millions of people in the U.S. Currently, there are only a small number of approved non-surgical treatments that exist for SCC."

This interim report of unblinded results of part-one of the Phase IIb study showed that 25 of 32 subjects with STP705 treatment resulted in a high ratio (78%) of histological clearance. Among three treatment cohorts, the 30 μg treatment group (N = 9) achieved the highest histological clearance (89%), while the 60 μg treatment group (N = 12) achieved 75%, and the 90 μg group (N = 11) achieved 73%, which are clearly higher than the placebo group (N = 12) which achieved 58%. There were no treatment-related AE’s or SAE’s and Local Skin Response Scores were stable or improved across all treatment groups.

About Non-melanoma Skin Cancer

Non-melanoma skin cancers (NMSC) are the most common forms of human neoplasia. NMSC constitute a large group of skin cancers that are not melanoma, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Extramammary Paget’s Disease (EMPD), Merkel cell carcinoma (MCC), and skin adnexal carcinomas. Among these, BCC and SCC account for the majority of NMSC with more than 5 million newly diagnosed cases estimated to occur in the U.S. every year. Along with BCC, SCC is one of two major subtypes of NMSC. NMSC treatment market in the U.S. is expected to increase from US$6.5 billion in 2020 to US$22 billion in 2030. In China, the market size of NMSC treatment was US$38 million in 2020 is also expected to grow faster in the coming years, reaching US$149 million in 2030.

A World Health Organization authorized report from "International Agency for Research on Cancer" (2019) has demonstrated that the number of deaths in 2018 globally for both men and women from NMSC is 65,155, where the mortality of Asia NMSC subjects represents 41.9% of the global total, which is significantly more than other individual areas.

Surgery is currently the most common treatment option for the treatment of NMSC. The various forms of surgical modalities carry significant cutaneous adverse events, risk of scar, infection and bleeding. As a result, there is a high unmet need for an FDA approved local injection therapy that is safe and effective.

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 U.S. Food and Drug Administration (FDA) and the Chinese National Medical Products Administration (NMPA), including treatments of cholangiocarcinoma, non-melanoma skin cancer and hypertrophic scar. STP705 has also received Orphan Drug Designation for treatment of cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC). STP705 is currently in seven clinical trials for different indications: a Phase IIb for squamous cell carcinoma in situ (isSCC), a Phase II for basal cell carcinoma (BCC), a Phase I/II for keloid scarring, a Phase I/II for hypertrophic scar (HTS), a Phase I/II for facial isSCC, a Phase I for liver cancer (basket), and a Phase I for medical aesthetics treatment.

On December 14, 2022 Solve Therapeutics, Inc. (SolveTx), an oncology-focused biopharmaceutical company, reported its mission to develop novel antibody-based therapies targeting tumor-specific antigens (Press release, Solve Therapeutics, DEC 14, 2022, View Source [SID1234625279]). The company’s formation reunites the former VelosBio Inc. (VelosBio) team, a highly experienced group with a proven ability to rapidly advance innovative therapeutics that address unmet medical needs in the treatment of cancer. SolveTx is supported by an accomplished board of directors and a top-tier investor syndicate. The company is fully operational with 25+ employees and is actively pursuing discovery and development efforts at its 10,000-square-foot, state-of-the-art laboratory in San Diego.

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SolveTx’s management team is headed by Chief Executive Officer (CEO) Dave Johnson. In previous roles as CEO, Mr. Johnson oversaw the development of a best-in-class Bruton’s tyrosine kinase inhibitor, acalabrutinib, at Acerta Pharma (established in 2012 and acquired by AstraZeneca for $7B in 2016) and a first-in-class, anti-ROR1 ADC, zilovertamab vedotin, at VelosBio (established in 2017 and acquired by Merck for $2.8B in 2020). The founding members of SolveTx from VelosBio who have worked with Mr. Johnson to establish the new company include Langdon Miller, MD, Executive Vice President of Development and Chief Medical Officer; Brian Lannutti, PhD, Executive Vice President of Research; Jeff Watkins, PhD, Senior Vice President, Protein Technology; and Katti Jessen, PhD, Senior Vice President, Translational Sciences. Collectively, SolveTx management possesses extensive expertise in drug discovery, development candidate selection, investigational new drug application (IND)-enabling evaluation, clinical trial conduct, and business development.

SolveTx’s initial $126 million Series A financing was completed with a syndicate of top-tier venture capital firms including Matrix Capital Management, Decheng Capital, General Atlantic, and Surveyor Capital/Citadel, each represented on the company’s board of directors.

"I am delighted to reassemble this highly collaborative and successful team of drug developers," said Dave Johnson, CEO of SolveTx. "Together with this incredible group of investors, we are empowered to apply our expertise and resources toward the ultimate goal of prolonging and improving the lives of patients with cancer."

SolveTx will use the proceeds for production of antibody-based therapeutics for nonclinical POC characterization, producer cell line generation, good manufacturing practices (GMP) drug production, IND-enabling pharmacology and toxicology studies, and Phase 1 clinical program initiation.

The foundation of SolveTx’s approach to oncology therapeutics development is the identification of novel cancer-specific targets and the generation of mAbs with ideal characteristics to serve as the backbones for antibody-based therapeutics. The company has signed a licensing agreement with the University of California San Diego for a series of antibodies that show high reactivity with tumors and no or low reactivity with normal tissues, which may enable the selective killing of tumor cells and a broad therapeutic index. SolveTx is reviewing other potential in-licensing opportunities as well as performing in-house antibody discovery research. The company’s focus is on the development of novel mAbs, ADCs incorporating next-generation linker and payload constructs, and bispecific antibodies.

On December 14, 2022 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported that it priced an underwritten public offering of 3,250,000 of its ordinary shares at a price to the public of $56.50 per ordinary share, before the underwriting discount and estimated offering expenses (Press release, Prothena, DEC 14, 2022, View Source [SID1234625277]). All of the ordinary shares in the offering were sold by Prothena. In addition, Prothena has granted the underwriters a 30-day option to purchase up to an additional 487,500 of its ordinary shares.

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Net proceeds to Prothena from the ordinary shares to be sold by Prothena in the offering are expected to be $172.4 million, after deducting the underwriting discount and estimated offering expenses, but excluding any exercise of the underwriters’ option to purchase additional ordinary shares. The offering is expected to close on December 19, 2022, subject to customary closing conditions.

Jefferies, Evercore ISI and Cantor are acting as lead book-running managers, Oppenheimer & Co. is acting as book-running manager and JMP Securities, a Citizens Company, and H.C. Wainwright & Co. are acting as co-lead managers for the offering.

The public offering is being made pursuant to an automatic shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission (the "SEC") on March 23, 2021 and automatically became effective upon filing. A final prospectus supplement and accompanying prospectus relating to and describing the final terms of the offering will be filed with the SEC and available on the SEC’s website located at View Source or may be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, or by telephone at (877) 821-7388, or by e-mail at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, NY 10055, or by telephone at (888)474-0200, or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY 10022, or by e-mail at [email protected].

On December 14, 2022 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a clinical update for naxitamab and the Company’s SADA technology programs will be presented at the Company’s R&D event, which will take place today at 9 a.m. Eastern Time (Press release, Y-mAbs Therapeutics, DEC 14, 2022, View Source [SID1234625276]).

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Investors, analysts, members of the media and the public may access the event via a live webcast. The presentation materials can be found on the Company’s website under the Presentations tab under the heading For Investors.

The Y-mAbs research and development day will feature presentations from Thomas Gad, founder, President and Interim-CEO, Vignesh Rajah, MBBS, DCH, MRCP(UK), MBA, (SVP, Chief Medical Officer at Y-mAbs), and Steen Lisby, M.D., DMSc, (SVP, Chief Scientific Officer at Y-mAbs).

SADA Technology

Dr. Lisby will discuss the Company’s SADA Technology, including announcement of the Company’s first proprietary hematological SADA construct, CD38-SADA against Non-Hodgkin’s Lymphoma ("NHL"), and an update on GD2-SADA, which is being studied in an ongoing Phase 1 clinical trial in adults with small-cell lung cancer, sarcoma, and malignant melanoma.

DANYELZA (naxitamab-gqgk)

Dr. Rajah, will present an update on DANYELZA (naxitamab-gqgk), including potential label expansion into osteosarcoma, and a planned multicenter Phase 2 trial in patients with newly diagnosed high-risk neuroblastoma.

"We are excited to share these new updates on both our naxitamab program and the SADA Technology. We believe that the prospects for the SADA Technology, which combines antibodies and radioactive payloads, are highly encouraging and could potentially revolutionize cancer treatments known today. We believe a CD38-SADA construct will have high potential," said Thomas Gad, founder, President and Interim CEO. "We are redoubling our efforts and refining our focus on DANYELZA and are pleased to be working towards advancing the program with a potential label expansion into osteosarcoma, and a planned multicenter Phase 2 trial in patients with newly diagnosed high-risk neuroblastoma."

Researchers at Memorial Sloan Kettering Cancer Center ("MSK") developed DANYELZA, which is exclusively licensed by MSK to Y-mAbs. MSK has institutional financial interests related to the compound and Y-mAbs.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information for complete Boxed Warning and other important safety information.