On November 23, 2020 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported clinical and regulatory progress by multiple partners utilizing antibodies from its OmniAb discovery platform (Press release, Ligand, NOV 23, 2020, View Source [SID1234571570]). Two large multinational pharmaceutical companies with a license to OmniAb have reached clinical-development milestones with their programs. The progress by these companies resulted in a total of $4.5 million in milestone payments being earned by Ligand.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition, CStone Pharmaceuticals recently announced that China’s National Medical Products Administration has accepted for review CStone’s New Drug Application (NDA) for sugemalimab (CS1001), an OmniAb-derived anti-PD-L1 monoclonal antibody used in combination with chemotherapy for the first-line treatment of advanced squamous and non-squamous non-small cell lung cancer (NSCLC). This marks the first regulatory submission by CStone for sugemalimab. Last month, CStone announced a major financial and commercial partnership with Pfizer to commercialize sugemalimab in greater China. Ligand is entitled to a 3% royalty on worldwide commercial sales of sugemalimab.

CStone also announced that positive clinical data based on a pre-planned interim analysis of the GEMSTONE-302 clinical study were disclosed in an oral presentation at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Virtual Congress 2020 on November 21, 2020 (link to full release here). The GEMSTONE-302 trial is the first randomized, double-blind, Phase 3 study of an anti-PD-L1 monoclonal antibody plus platinum-based chemotherapy as first-line treatment for stage IV squamous or non-squamous NSCLC. The results showed sugemalimab plus chemotherapy as first-line treatment for advanced NSCLC demonstrated statistically significant and clinically meaningful benefit in progression free survival (PFS) compared to chemotherapy across PD-L1 expression levels and histologies. Specifically, sugemalimab in combination with chemotherapy reduced the risk of disease progression or death by 50% and produced an objective response rate (ORR) of 61.4%. The combination therapy was well-tolerated with no new safety signals detected. CStone reported that these Phase 3 data are amongst the best of those reported by other anti-PD-L1 monoclonal antibodies.

"We are very pleased with the progress and impressive data our partners are reporting with their Ligand OmniAb-derived antibodies," said John Higgins, Chief Executive Officer of Ligand. "There are currently more OmniAb programs than ever under development, and as programs advance Ligand is now collecting more and larger milestone payments that are contributing to our strong financial performance. Next year we anticipate the first two OmniAb-derived antibodies could receive regulatory approvals, and these events could start the first OmniAb royalty revenue to Ligand. With partnership and royalty rights on programs that extend to 2040 and beyond, we believe we are in the early days of a substantial growth trajectory from our OmniAb business."

About OmniAb

OmniAb is a three-species transgenic-animal platform consisting of five different technologies used for producing mono- and bispecific human therapeutic antibodies. OmniRat animals comprise the industry’s first human monoclonal antibody technology based on rats. Because they have a complete immune system with a diverse antibody repertoire, OmniRat animals generate antibodies with human idiotypes as effectively as wild-type animals make rat antibodies. OmniMouse is a transgenic mouse that complements OmniRat and expands epitope coverage. OmniFlic is an engineered rat with a fixed light chain for development of bispecific, fully human antibodies. OmniChicken animals comprise the industry’s first human monoclonal antibody technology based on chickens. The OmniClic chicken is specifically developed to facilitate the generation of bispecific antibodies and retains the ability to generate diverse, high quality affinity matured antibodies. All five types of OmniAb therapeutic human antibody platform, OmniRat, OmniFlic, OmniMouse, OmniChicken and OmniClic, use patented technology, have broad freedom to operate, produce highly diversified, fully human antibody repertoires optimized in vivo for immunogenicity, manufacturability, and therapeutic efficacy, and deliver fully

On November 23, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the filing of an Investigational New Drug application (IND) with the U.S. Food and Drug Administration (FDA) for ON 123300, the Company’s proprietary, differentiated, first-in-class multi-kinase inhibitor (Press release, Onconova, NOV 23, 2020, View Source [SID1234571568]). The IND seeks permission to begin a Phase 1 trial with ON 123300 in relapsed/refractory advanced cancer including patients with HR+ HER 2- metastatic breast cancer with resistance to approved second-generation CDK4/6 inhibitors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We believe that ON 123300, based on its novel mechanism of action, presents an innovative approach to study advanced cancers including in HR+ HER 2- metastatic breast cancer that is or has become resistant to commercial CDK4/6 inhibitors. We are delighted to have filed our IND on schedule, and look forward to enrolling patients in the U.S. to complement the ongoing Phase 1 dose-escalation study underway in China by our partner HanX Biopharmaceuticals," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "The HanX Phase 1 ON 123300 study, which began in September 2020, has enrolled three patients to date and is expected to continue to enroll patients with advanced relapsed/refractory cancer at two sites until the recommended Phase 2 dose is identified. We believe that data from these two studies will generate important information to inform anticipated later-stage studies."

As currently envisioned, the Phase 1 trial in the U.S. will assess the safety, tolerability, and pharmacokinetics of ON 123300 administered orally as monotherapy at increasing doses starting at 40 mg daily or higher for consecutive 28-day cycles. The Phase 1 trial is planned for patients with relapsed/refractory advanced cancer, including but not limited to patients with HR+ HER 2- metastatic breast cancer with clinical resistance to the approved second-generation CDK4/6 inhibitors. Once the recommended Phase 2 dose is established, the Company’s plan is to enroll additional HR+ HER 2- postmenopausal metastatic breast cancer patients refractory to approved second-generation CDK4/6 inhibitors, as well as patients diagnosed with advanced non-Hodgkin’s lymphoma with a special interest in mantle cell lymphoma.

This trial design in the U.S. differs from the study in China because HanX is dosing patients daily for 21 days. Notably, of the three currently approved CDK4/6 inhibitors, two are approved for dosing in 21-day cycles and one is approved for dosing in a 28-day cycle. All three are blockbuster drugs marketed by well-known pharmaceutical companies, and all of these approved therapies require concomitant treatment with an aromatase inhibitor.

"Beyond metastatic breast cancer, we believe that ON 123300 may present an innovative approach to treating other cancers including mantle cell lymphoma, multiple myeloma, advanced colorectal cancer, advanced hepatocellular carcinoma, and inoperable glioblastoma based on preclinical studies suggesting ON 123300 crosses the blood-brain barrier," added Richard Woodman, M.D, Chief Medical Officer.

Commenting on the expected timetable and next steps with this program, Dr. Fruchtman added: "Once the FDA approves our IND, we will seek Institutional Review Board approval at the site where this Phase 1 trial will be conducted. We anticipate the first patient to be enrolled during the first half of 2021. With the ON 123300 program advancing, investigator-sponsored trials underway with our pipeline product rigosertib, and an active business development campaign to evaluate additional compounds, we look forward to an expanding portfolio of novel therapeutics for large, underserved oncology indications."

About ON 123300

Onconova’s lead pipeline product is the novel small molecule ON 123300, a proprietary, first-in-class multi-kinase inhibitor targeting tumor-driving kinases including CDK4/6 and ARK5. ON 123300 is reported to simultaneously inhibit both cell cycle and cellular energy metabolism through CDK4/6 and ARK5, respectively, and in vitro has been shown to be cytotoxic to cancer cells (killing the cancer cells) rather than just cytostatic (inhibiting the growth of cancer cells), which is how the currently commercial CDK inhibitors are reported to work. With its differentiated mechanism of action, ON 123300 may present an innovative approach for treating solid tumors and hematologic malignancies that are refractory to or have become resistant to other CDK4/6 inhibitors.

Based on experiments in preclinical models, ON 123300 exhibits single-agent cytotoxicity, may have utility for certain types of cancers including breast cancer and non-Hodgkin’s lymphoma, and may also have utility for mantle cell lymphoma, multiple myeloma, advanced colorectal cancer, advanced hepatocellular carcinoma, and inoperable glioblastoma.

On November 23, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported the publication of clinical data that provides molecular insight into TRC102’s mechanism of action and patient populations most likely to respond to treatment (Press release, Tracon Pharmaceuticals, NOV 23, 2020, View Source [SID1234571567]). The article, entitled, "Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment," highlights the clinical features and tumor biology of an exceptional responder patient treated with TRC102 at the National Cancer Institute (NCI): View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The patient was diagnosed with metastatic and highly refractory colorectal cancer and received temozolomide (Temodar) and TRC102. Following treatment, the patient was considered an exceptional responder through the achievement of a near compete response lasting 45 months at the most recent follow-up. Detailed molecular analyses of the patient’s tumor showed silencing of DNA repair pathways that may have resulted in sensitivity to the inhibition of DNA base excision repair pathway by TRC102. Specifically, MGMT expression was silenced by promoter methylation, and RAD50, a mediator of DNA double strand break repair, was silenced by genetic mutation and loss of heterozygosity. The publication authors hypothesized that the combination of Temodar and TRC102 was effective because all necessary DNA repair pathways were compromised genetically or through the activity of TRC102. MGMT expression was also assessed in biopsies from 11 colorectal patients who subsequently enrolled in an expansion cohort, one of which demonstrated a partial response. The tumor associated with the partial response did not express MGMT, whereas each of the 10 tumors that did not respond to therapy expressed this enzyme robustly.

TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the NCI through a Cooperative Research and Development Agreement. TRC102 was also evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent glioblastoma who progressed following Temodar and external beam radiotherapy. Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and showed hyperactivation of DNA damage response genes prior to treatment with TRC102.

"The Cancer Cell publication supports our belief that patients whose cancers are dependent on the DNA base excision repair pathway to repair DNA damage from chemotherapy may be particularly sensitive to the pharmacologic effects of TRC102," said James Freddo, M.D., Chief Medical Officer of TRACON. "The NCI data are also consistent with the results from the Phase 2 trial of Temodar and TRC102 in refractory glioblastoma. We remain committed to developing TRC102 in collaboration with the NCI and believe that the data generated to date provide strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma."

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage 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). TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.

About Malignant Glioma and GBM

GBM (also called glioblastoma) is a fast-growing malignant glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults (12,630 men and 10,280 women) are diagnosed with brain and other nervous system cancer annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.

On November 23, 2020 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that it will present and participate at the following virtual conferences in December (Press release, RedHill Biopharma, NOV 23, 2020, View Source [SID1234571566]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Evercore ISI 3rd Annual HealthCONx Conference
Fireside chat and an open Q&A: Thursday, December 3, 2020, 8 a.m. EST
Moderator: Umer Raffat, Equity Research – Biotech-large, Pharma-major, Specialty Pharma
Speaker: Dror Ben-Asher, CEO & Gilead Raday, Chief Operating Officer

Piper Sandler 32nd Annual Virtual Healthcare Conference
Fireside chat: Available on-demand from November 23, 2020
Moderator: David Amsellem, Managing Director, Sr. Research Analyst, Specialty Pharma
Speaker: Guy Goldberg, Chief Business Officer

The webcasts will be available for replay for 30 days on the Company’s website: View Source

On November 23, 2020 Silicon Therapeutics, a privately-held, integrated therapeutics company with a pioneering platform based on physics-driven molecular simulations, reported treatment of the first patient with its therapeutic candidate SNX281 in a Phase 1 clinical trial in patients with advanced solid tumors or lymphoma (Press release, Silicon Therapeutics, NOV 23, 2020, View Source [SID1234571564]). Wholly owned by Silicon Therapeutics, SNX281 is a small molecule Stimulator of Interferon Genes (STING) agonist with systemic exposure that was designed using unique insights and capabilities provided by the Silicon Therapeutics proprietary physics-driven drug discovery platform.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This Phase 1 open-label, multicenter, multidose, first-in-human clinical trial of SNX281 will evaluate the safety and tolerability of SNX281 alone and in combination with the PD-1 inhibitor pembrolizumab in subjects with relapsed or refractory solid tumors or lymphomas. The trial is designed to enroll up to 128 patients.

"The initiation of this study is a significant milestone for Silicon Therapeutics, as it marks the entry of our lead therapeutic into clinical development. The speed with which we have arrived at this milestone from our foundation in 2016 is a testament to Silicon Therapeutics’ unique platform. Computational physics-driven drug discovery has truly come to fruition with our delivery of this new experimental medicine," said Lanny Sun, co-founder and chief executive officer. "As we navigate the unprecedented COVID-19 pandemic, we are leveraging virtual capabilities to initiate clinical trial sites, while ensuring patient and clinician safety is our top priority. We are incredibly grateful to the patients and their families, investigators and their clinical study sites, and our employees for advancing a program with the potential to treat patients suffering from challenging and life-threatening cancers."

The company’s proprietary platform is being used to design additional first-in-class small molecules targeting key drivers of disease in cancer that have proven difficult to treat with prior approaches and thus previously considered undruggable. The discovery platform is fully integrated with Silicon Therapeutics’ internal laboratories using cutting edge experimental capabilities in biophysics, biology and chemistry.

"There have been important advancements in immunotherapy treatments for cancer in recent years, but many patients do not benefit and therefore new approaches to stimulate effective anti-tumor responses are needed in the clinic," said Humphrey Gardner, M.D., F.C.A.P, chief medical officer. "We are excited about the potential of SNX281 to treat a broad array of cancers given its strong pre-clinical activity both as a single agent and in combination with a PD-1 inhibitor. We look forward to sharing the near- and long-term data as it becomes available."

About the SNX281 Clinical Trial
The purpose of this Phase 1 multi-center, open-label study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical activity of SNX281 as a monotherapy and in combination with pembrolizumab, a monoclonal antibody immunotherapy for the treatment of cancers. Dose escalation in monotherapy and combination will be explored in patients with advanced solid tumors or lymphoma. After determination of the optimal dose of SNX281 as a single-agent and in combination with pembrolizumab, expansion cohorts to further evaluate safety and efficacy in specific populations will be examined, including colorectal and ovarian carcinoma in the monotherapy arm, and tumors refractory to or relapsed on checkpoint inhibitors in the combination arm.

For more information about the SNX281 clinical trial (NCT04609579), please visit: View Source

About SNX281
Activation of STING provides two critical anti-tumor responses: the "spark" for initiating a robust innate immune response as well as the priming and induction of a robust tumor directed T cell response, providing sustained antitumor immunity. First generation clinical compounds are structural mimetics of endogenous cyclic dinucleotides (CDNs) STING agonists and cannot be delivered systemically, thus limiting use to local delivery via intra-tumoral injection.

To address these limitations, the Silicon Therapeutics team has designed and developed the small molecule STING agonist SNX281 with unique drug properties permitting systemic delivery. SNX281 is potent, specific and active against all prevalent human isoforms of STING, rapidly activating downstream signaling and induction type I interferon (IFN). Treatment of primary immune cells from human donors results in the maturation and activation of antigen presenting cells. In vivo, SNX281 stimulates cross-presentation, antigen-specific T cell response and rapid multi-lineage anti-tumor immunity.

In preclinical disease models, treatment with SNX281 results in complete regression of tumors in mice harboring colorectal tumors (CT26) with a single intravenous dose. This anti-tumor activity was shown to be immune-mediated, as it did not occur in immunocompromised mice. Further, the combination of an anti-PD-1 antibody with SNX281 demonstrated both enhanced anti-tumor activity as well as increased survival in a variety of additional tumor models.

SNX281 drug characteristics and STING pharmacology allow for a unique dosing paradigm with robust tumor regression after a short duration of exposure, and durable anti-tumor immunity.