On December 17, 2021, Oncternal Therapeutics, Inc. ("Oncternal") reported that it entered into an Open Market Sale AgreementSM (the "Sale Agreement") with Jefferies LLC (the "Agent"), pursuant to which Oncternal may offer and sell shares of Oncternal’s common stock having an aggregate offering price of up to $50,000,000 from time to time, in "at the market" offerings through the Agent (Filing, 8-K, Oncternal Therapeutics, DEC 17, 2021, View Source [SID1234597410]). Sales of the shares of common stock, if any, will be made at prevailing market prices at the time of sale, or as otherwise agreed with the Agent. The Agent will receive a commission from Oncternal of 3.0% of the gross proceeds of any shares of common stock sold under the Sale Agreement.

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!

Oncternal is not obligated to sell, and the Agent is not obligated to buy or sell, any shares of common stock under the Sale Agreement. No assurance can be given that Oncternal will sell any shares of common stock under the Sale Agreement, or, if it does, as to the price or amount of shares of common stock that it sells or the dates when such sales will take place.

In the Sale Agreement, Oncternal agreed to indemnify the Agent against certain liabilities, including under the Securities Act of 1933, as amended, or to contribute payments that the Agent may be required to make because of such liabilities.

The shares of common stock sold pursuant to the Sale Agreement will be offered pursuant to a shelf registration statement on Form S-3 (File No. 333-254985), which became effective on April 15, 2021. Oncternal filed a prospectus supplement with the U.S. Securities and Exchange Commission on December 17, 2021 in connection with the offer and sale of shares of Oncternal’s common stock pursuant to the Sale Agreement.

A copy of the Sale Agreement is attached as Exhibit 1.1 hereto and is incorporated herein by reference. The foregoing description of the Sale Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sale Agreement.

A copy of the opinion of Latham & Watkins LLP relating to the validity of the shares of common stock that may be sold pursuant to the Sale Agreement is filed herewith as Exhibit 5.1.

On December 17, 2021 Genoscience Pharma, a clinical stage biotechnology company developing unique lysosomotropic drug candidates for the treatment of cancer, auto-immune and infectious diseases through autophagy modulation, reported the licensing of its PPT-1 inhibitor, GNS561, in cholangiocarcinoma indication, to GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and chronic liver diseases (Press release, GenoScience, DEC 17, 2021, View Source [SID1234597409]). GENFIT will develop and commercialize investigational treatment with GNS561 in cholangiocarcinoma, in the United States, Canada and Europe, including the United Kingdom and Switzerland.

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!

Under the agreement, GENFIT is committed to taking a €3 million ($3.4M) equity stake in Genoscience Pharma through the subscription of new ordinary shares. GENFIT will also contribute clinical and regulatory milestone payments and tiered royalties (financial terms not disclosed). The first payable milestone is contingent on positive results from the phase 2 clinical trial in cholangiocarcinoma, which is expected to start in the first half of 2022.

GNS561 is a novel clinical-stage autophagy/PPT1 inhibitor developed by Genoscience Pharma in cholangiocarcinoma indication, which is an orphan disease. The inhibitor has completed preclinical studies and a phase 1b trial confirming the rationale for targeting cholangiocarcinoma, a rare liver malignancy with high mortality and with limited treatment options.

"This is a great step for the development of GNS561 as a new potential treatment option in liver cancer, as it offers an innovative mechanism of action for patients with high unmet needs," said Philippe Halfon, CEO of Genoscience Pharma. "We believe that GENFIT is a highly qualified partner for the development of GNS561 in cholangiocarcinoma and we will provide GENFIT with our expertise in oncology to support their development plan. On our side, we will pursue the development of GNS561 in other oncology indications as well as research in other therapeutic areas."

"This decision fully aligns with our strategic roadmap by broadening our asset portfolio within our cholestatic disease franchise, through the addition of an innovative drug candidate with the potential to address considerable unmet needs for patients," said Pascal Prigent, CEO of GENFIT. "The scientific rationale, together with preclinical and clinical evidence, supports further development of the asset, and our plan is to start the phase 2 program in the first half of 2022. We believe that GNS561’s mechanism of action is very promising. Given the current landscape, standard of care and lack of marketed options, and based on KOL opinions, we will interact with regulatory agencies to investigate accelerated paths to approval, post phase 2."

About cholangiocarcinoma
Cholangiocarcinoma is a type of cancer that forms in the slender tubes (bile ducts) that carry the digestive fluid bile. Cholangiocarcinoma occurs mostly in people over the age of 50. Cholangiocarcinoma is divided into intrahepatic and extrahepatic types based on where the disease occurs in the bile ducts. Cholangiocarcinoma is often diagnosed when it is advanced, making successful treatment difficult to achieve. Several risk factors of chronic inflammatory damage and increased cellular turnover have been established, such as primary sclerosing cholangitis, a cholestatic liver disease, liver flukes, biliary tract cysts, hepatolithiasis and toxins. Treatment options for cholangiocarcinoma are limited and associated with high rates of tumor recurrence and short survival times.

About GNS561
GNS561 is a PPT-1 (Palmitoyl Protein Thioesterase-1) inhibitor that blocks autophagy. Autophagy is activated in tumor cells in response to certain conditions, due to tumor cell growth in advanced cancers. One of the key organelles implicated in the autophagy process is the lysosome. By entering the lysosome and binding to its target, GNS561 has an important inhibiting activity on late-stage autophagy, which leads to tumor cell death. GNS561 is an investigational compound and has not been registered by any regulatory authority.

On December 17, 2021 Senhwa Biosciences, Inc. (TPEx: 6492), a drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and novel coronaviruses, reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for Silmitasertib, a highly selective inhibitor of casein kinase 2 (CK2) to treat patients with Medulloblastoma (Press release, Senhwa Biosciences, DEC 17, 2021, View Source [SID1234597382]).

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 FDA grants ODD status to drugs and biologics that are intended to treat, prevent or diagnose a rare disease or condition with a prevalence of fewer than 200,000 people in the U.S. ODD affords certain financial incentives to support clinical development, exemption from user fees and the potential for up to seven years of market exclusivity in the U.S. upon marketing approval.

"We are pleased to receive ODD for Silmitasertib for Medulloblastoma, a rare, severe pediatric disease for which there are no approved targeted therapies. ODD represents an important regulatory milestone that has the potential to expedite the clinical development of Silmitasertib, a potent and selective CK2 inhibitor," said Dr. John Soong, Chief Medical Officer of Senhwa Biosciences.

Senhwa’s clinical partner, the Pediatric Brain Tumor Consortium (PBTC, www.pbtc.org), is currently conducting a Phase I/II and Surgical Study of Silmitasertib in both children and adults with recurrent sonic hedgehog (SHH) () driven Medulloblastoma. This study is taking place at the PBTC’s participating member academic medical centers and children’s hospitals across the United States. The PBTC is sponsoring this clinical trial and is funded through the Consortium grant awarded by the US National Institute of Health – Cancer Therapy Evaluation Program (CTEP).

Medulloblastoma is the most common cancerous brain tumor in children, but no targeted therapy is currently available. In addition to ODD, Silmitasertib was granted Fast Track Designation and Rare Pediatric Disease (RPD) Designation from the US FDA on Aug 17, 2021 and July 6, 2020, respectively. If certain criteria are met with the RPD Designation, Senhwa would be eligible for a transferrable Priority Review Voucher (PRV). The PRV allows its recipient an expedited review process of any one of its new drug products from a ten-month to a six-month timeframe.

About Silmitasertib

Silmitasertib is a first-in-class small molecule drug that targets the CK2 pathway and acts as a CK2-inhibitor. Clinical studies thus far have shown CX-4945 to be well-tolerated in humans. In addition to COVID-19, Silmitasertib is currently under development in several oncology programs in adults and children with recurrent/advanced or metastatic cancer. To date, three Phase I trials and one Phase II trial of Silmitasertib in cancer patients have been completed; currently, there are two ongoing Phase II studies of Silmitasertib. The US FDA granted Silmitasertib key drug designations: Orphan Drug Designation for the treatment of Cholangiocarcinoma in December 2016, Rare Pediatric Disease Designation in July 2020 for the treatment of Medulloblastoma, Fast Track Designation in August 2021 for the treatment of recurrent Sonic Hedgehog driven Medulloblastoma and an eIND for the treatment of a patient with severe COVID-19 in August 2020.

On December 17, 2021 Antengene Corporation Limited (the "Company" or "Antengene") reported that ATG-010 (selinexor, brand name: XPOVIO), a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound has received conditional approval for marketing by the National Medical Products Administration (the "NMPA"), applicable in combination with dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have received prior therapy including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. XPOVIO is China’s first approved XPO1 inhibitor (Press release, Antengene, DEC 17, 2021, View Source [SID1234597380]). The conditional approval of XPOVIO was based on the global Phase 2 STORM trial as well as the positive results from the Phase 2 MARCH trial. The ongoing, randomized Phase 3 BENCH study in China, evaluating selinexor in combination with bortezomib and low-dose dexamethasone for patients with multiple myeloma as early as first relapse, will serve as the confirmatory trial.

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!

Antengene will host conference calls for investors on December 20, 2021 (China Standard Time).

Dr. Jay Mei, M.D., Ph.D., Chairman and Chief Executive Officer of Antengene commented, "Our mission is to bring first-in-class/best-in-class medicines to the market for patients with cancer and other life-threatening diseases. I am pleased that XPOVIO is Antengene’s first product to be approved in China and the first and only XPO1 inhibitor on the market in China."

Dr. Mei continued, "We believe the approval of XPOVIO will bring important clinical benefits to Chinese patients with refractory or relapsed multiple myeloma. XPOVIO is approved in three indications in the U.S., including in second line multiple myeloma, and the product has been widely adopted into practice guidelines by major oncology networks including the Chinese Society of Clinical Oncology (CSCO) in China, the National Comprehensive Cancer Network (NCCN) in the U.S. and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in the EU. These are very positive steps to enabling product acceptance and adoption."

Dr. Kevin Lynch, M.D., Chief Medical Officer of Antengene commented, "With XPOVIO’s approval in China, Antengene can offer a new, much needed therapeutic option to Chinese patients with RRMM. We believe selinexor has broad potential in oncology and are committed to advance further development of the product though our program of 10 clinical studies in China. These include the confirmatory Phase 3 BENCH study for multiple myeloma patients after at least one prior therapy, as well as studies in other oncology indications that have strong relevance for patients in China."

Dr. Lynch continued, "Antengene would like to thank all of the patients and investigators involved in the clinical study and the NMPA for their support during the priority review. Together, we are aiming to improve the care and lives of people with cancer in China and around the world."

Antengene Conference Call Details

Antengene management will hold conference calls on Monday, December 20, 2021 to discuss the approval in China of ATG-010/XPOVIO:

Pivotal STORM and MARCH Trials

The conditional approval of XPOVIO was based on results from the global Phase 2 STORM trial as well as the Phase 2 MARCH trial in China evaluating the efficacy and safety of selinexor plus dexamethasone in 82 patients with relapsed/refractory multiple myeloma (RRMM).

Results of the STORM trial showed that the overall response rate (ORR), the primary endpoint, as assessed by an Independent Review Committee (IRC), based on the International Myeloma Working Group (IMWG) Uniform Response Criteria, was 25.3% for the prespecified subgroup of 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.

Results of the MARCH trial showed that the efficacy and safety in Chinese patients whose disease was refractory to both lenalidomide and bortezomib, as well as the last line of therapy (with some also refractory to anti-CD38 monoclonal antibody), were generally consistent with that seen in the global study. The overall response rate, the primary endpoint, as assessed by an Independent Review Committee (IRC), was 29.3%, for all treated patients in the MARCH trial and 25% for patients refractory to at least a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

The ongoing, randomized Phase 3 BENCH study evaluating selinexor in combination with bortezomib and low-dose dexamethasone will serve as the confirmatory trial.

About the SINE Compounds

SINE (Selective Inhibitor of Nuclear Export) compounds are inhibitors of the major nuclear export protein Exportin 1 (XPO1). Currently, there are three oral SINE compounds, ATG-010 (selinexor), ATG-016 (eltanexor), and ATG-527 (verdinexor), under clinical development. Antengene has an exclusive license from Karyopharm Therapeutics Inc. ("Karyopharm") to these compounds in certain APAC markets.

About ATG-010/Selinexor/ XPOVIO

Selinexor is the first and only oral XPO1 inhibitor approved by the U.S. Food and Drug Administration (FDA). By blocking the nuclear export protein XPO1, selinexor can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. This induces apoptosis without affecting normal cells. Due to its novel mechanism of action, selinexor is being evaluated for use in multiple combination regimens to improve treatment efficacy.

Selinexor is approved by the U.S. FDA for the treatment of relapsed/refractory multiple myeloma (RRMM), second line multiple myeloma and relapsed/refractory diffuse large B–cell lymphoma.

Antengene obtained approval of selinexor in South Korea through a priority review process prior to the current approval by NMPA in China. Antengene is conducting 10 studies with selinexor in mainland China (3 in collaboration with Karyopharm) for relapsed/refractory/advanced hematological malignancies and advanced solid tumors.

On December 17, 2021 TRANSGENE (Paris:TNG) reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, DEC 17, 2021, View Source [SID1234597379]).

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!

Transgene will meet institutional investors at the 11th Annual LifeSci Advisors Corporate Access Event (virtual event) from January 5th to 7th, 2022.

The Company will also attend:

25th ODDO BHF Digital Forum (virtual): January 6, 7, 10 and 11, 2022
Biotech Showcase Investor Conference (virtual):
January 10 to 12, 2022, in conjunction with the J.P. Morgan Healthcare conference
January 17 to 19, 2022
Biomed Event (Paris): January 26, 2022