On January 10, 2021 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to create product candidates that address unmet medical needs, reported that it will provide an update on Vision 3×3 and the company’s 2021 key milestones at the 39th Annual J.P. Morgan Healthcare Conference (Press release, Ascendis Pharma, JAN 10, 2021, View Source;3-update-39th-annual-jp-morgan [SID1234573750]).

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 2019, we introduced Vision 3×3, the company’s strategic roadmap through 2025, to build a leading biopharma company by achieving sustainable growth through multiple approaches. 2020 was a remarkable year of progress for Ascendis reflecting the dedication and commitment of our employees worldwide as we made meaningful strides to achieve our vision, and meet or accelerate completion of our key milestones," said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer.

"We expect 2021 will mark a number of key clinical and commercial milestones. By the end of the year, we expect to have five independent TransCon product candidates in clinical development leveraging TransCon technologies through our algorithm for product innovation. We expect to further advance our late stage endocrinology pipeline with the anticipated approval and launch in the United States and the approval in Europe of TransCon hGH for pediatric growth hormone deficiency, and to obtain phase 3 results for TransCon PTH in adult hypoparathyroidism. Development of TransCon CNP is progressing as planned with the recent initiation by VISEN Pharmaceuticals of a second phase 2 trial in patients with achondroplasia, the ACcomplisH China Trial, which provides for dose expansion at an effective dose determined from the ACcomplisH Trial. Finally, we expect to have the first two product candidates from our second therapeutic area of oncology in clinical development," Mr. Mikkelsen added.

Pipeline Updates

•TransCon hGH (lonapegsomatropin): Lonapegsomatropin is an investigational long-acting prodrug of somatropin (human growth hormone or hGH) currently under review for use in pediatric growth hormone deficiency (GHD) by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA):
οThe company submitted its Biologic License Application to the FDA which has set a Prescription Drug User Fee Act (PDUFA) date for June 25, 2021. If approved on the PDUFA date, Ascendis anticipates commercial launch in the third quarter of 2021.
οThe company submitted its Marketing Authorisation Application (MAA) to the EMA in September 2020 and anticipates receiving MAA approval for lonapegsomatropin for use in pediatric GHD in the fourth quarter of 2021.
οAscendis anticipates completion of enrollment in foresiGHt, a global phase 3 trial evaluating the safety and efficacy of lonapegsomatropin in adult patients with GHD, by late 2021 or early 2022.

•TransCon PTH: TransCon PTH is an investigational long-acting prodrug of parathyroid hormone (PTH) in development as a potential once-daily replacement therapy for adult hypoparathyroidism (HP):
οFrom the PaTH Forward phase 2 trial, 58 out of 59 randomized subjects continue receiving TransCon PTH in the open label extension (OLE) as of January 5, 2021.
οAfter 26 weeks of follow-up in the PaTH Forward Trial, bone densitometry data from subjects treated with TransCon PTH demonstrated trends towards normalization of bone mineral density. In addition, quality of life as measured by the SF-36 Health Survey showed normalization of mean scores for all summary domains and all subdomains.
οDuring the second quarter of 2021, Ascendis expects to provide a 12-month OLE update and plans to submit a Clinical Trial Notification for a clinical trial evaluating TransCon PTH for adult HP in Japan.
οTop-line results from PaTHway, a phase 3 randomized, double-blind, placebo-controlled clinical trial in North America and Europe, investigating the safety, tolerability, and efficacy of TransCon PTH in adults with HP are expected in the fourth quarter of 2021.

•TransCon CNP: TransCon CNP, an investigational long-acting prodrug of C-type natriuretic peptide (CNP), as a potential therapeutic option for patients with achondroplasia (ACH):
οDosing of sequential ascending dose cohorts continues in the ACcomplisH Trial, a phase 2 randomized, double-blind, placebo-controlled clinical trial in North America, Europe, and Oceania.
οVISEN Pharmaceuticals (VISEN), our strategic investment in China, received approval from China’s Center for Drug Evaluation to conduct the ACcomplisH China Trial, a phase 2 randomized, double-blind, placebo-controlled clinical trial.
οAscendis expects that the ACcomplisH and ACcomplisH China Trials will enroll more than 120 subjects in total (ages 2-10), to be followed for 12 months.
οThe company plans to provide a TransCon CNP clinical program update in the fourth quarter of 2021.

•TransCon TLR7/8 Agonist: TransCon TLR7/8 Agonist is an investigational long-acting prodrug of resiquimod, a small molecule agonist of Toll-like receptors (TLR) 7 and 8 designed to provide sustained activation of intratumoral antigen-presenting cells driving tumor antigen presentation and induction of immune stimulatory cytokines for weeks or months with a single intratumoral injection:
οSubmitted IND to the FDA in December 2020 to initiate clinical program.
οDuring the second quarter of 2021, following monotherapy evaluation, the company plans to initiate TransCon TLR7/8 Agonist dose escalation in combination with a checkpoint inhibitor.
οInitial monotherapy dose escalation results are expected in the fourth quarter of 2021.

•TransCon IL-2 β/γ: TransCon IL-2 β/γ is an investigational novel long-acting prodrug of IL-2 β/γ designed to selectively bind and activate the IL-2Rβ/γ:
οAscendis reported pre-clinical data for TransCon IL-2 β/γ demonstrating:
•Independently optimized receptor bias and potency as well as pharmacokinetics to create a potentially best-in-class IL-2 product.
•An effective half-life of approximately 32 hours in non-human primates (NHP).
•Following a single dose of TransCon IL-2 β/γ in NHP, observed potential best-in-class expansion and activation of cytotoxic lymphocyte subsets with minimal effect on eosinophils, minimal IL-5 and IL-6 levels which suggests low risk of vascular leak syndrome.
οThe company expects to submit an IND or similar for TransCon IL-2 β/γ in the third quarter of 2021.

Global Endocrinology Rare Disease Commercial Strategy

In anticipation of regulatory approvals for lonapegsomatropin in the United States and Europe, Ascendis is establishing a global commercial presence through multiple approaches. This global commercial approach will be laying the groundwork for future potential endocrinology rare disease launches as TransCon PTH and TransCon CNP advance in clinical development.

The company’s US commercial organization is in place and commercial manufacturing is ongoing for the potential launch of lonapegsomatropin in pediatric GHD planned for the third quarter of 2021 after anticipated regulatory approval.

In addition, Ascendis is preparing for potential commercialization in Europe, building an integrated organization in select European countries and evaluating established distribution channels in other European countries to be ready for the anticipated MAA approval of lonapegsomatropin in pediatric GHD in the fourth quarter of 2021.

Lastly, Ascendis plans to serve patients in other regions around the world through established sales and distribution networks and following applicable regulatory approvals. The company has invested in VISEN in Greater China and plans to partner in Japan and South Korea when appropriate.

Presentation at J.P. Morgan Healthcare Conference on Monday, January 11th

Live webcast of the J.P. Morgan presentation will be available on the Events & Presentations section of the investor relations webpage at View Source The presentation will begin at 11:40 a.m. ET. A webcast replay will also be available for 30 days.

The company’s slides from the J.P. Morgan presentation will be available on the investor relations website.

About TransCon Technology Platform

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology to create new therapies that are designed to optimize therapeutic effect, including efficacy and safety and through dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. The TransCon technology platform can be applied broadly to proteins, peptides or small molecules in multiple therapeutic areas, and can be designed for systemic or localized release.

On January 9, 2021 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to create product candidates that address unmet medical needs, reported an equity investment of $12.5 million in VISEN Pharmaceuticals (VISEN) as part of VISEN’s $150 million Series B financing (Press release, Ascendis Pharma, JAN 9, 2021, View Source [SID1234573749]).

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!

"Our relationship with VISEN is a key element of our Vision 3×3 strategy to extend the global reach of our TransCon endocrinology rare disease product candidates and improve patients’ lives around the world," said Jan Mikkelsen, President and CEO at Ascendis Pharma. "Since VISEN’s inception in 2018, the company has made significant progress on its clinical activities in Greater China, which we believe will enable us to get our products to patients worldwide as soon as possible."

In 2018, Ascendis granted VISEN exclusive rights to develop and commercialize TransCon hGH (lonapegsomatropin), TransCon PTH and TransCon CNP in Greater China and received 50 percent ownership of VISEN’s issued and outstanding shares. Following VISEN’s Series B financing, Ascendis retains approximately 44 percent of VISEN’s issued and outstanding shares. As a result, Ascendis expects to recognize a non-cash gain in the first quarter of 2021.

Concurrent with the closing of the Series B financing, Michael Wolff Jensen, Chairman, Senior Vice President and Chief Legal Officer of Ascendis, became a member of VISEN’s board and serves as Chairman. Mr. Mikkelsen also will continue to serve on VISEN’s board.

"I look forward to joining the VISEN board and to working with the talented management team to accelerate the clinical pipeline of investigational TransCon drug candidates," said Mr. Jensen.

About VISEN Pharmaceuticals

VISEN Pharmaceuticals is committed to the treatment of endocrine-related diseases, introducing the world’s leading treatment methods and drugs into the China market and hoping to provide more Chinese patients quick access to the world’s most advanced and reliable treatment solutions.

In 2018, VISEN Pharmaceuticals (VISEN) was formed by Ascendis Pharma A/S (Nasdaq: ASND) and an investor syndicate led by Vivo Capital (along with participation by Sofinnova Ventures), to develop and commercialize endocrinology therapies in Greater China, which includes mainland China, Hong Kong, Macau, and Taiwan.

About TransCon Technology Platform

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology to create new therapies that are designed to optimize therapeutic effect, including efficacy and safety and through dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransCon technology can be applied broadly to proteins, peptides or small molecules in multiple therapeutic areas, and can be designed for systemic or localized release.

On January 08, 2021 Chimerix (NASDAQ:CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, reported that the Company has acquired Oncoceutics, Inc., a privately-held, clinical-stage biotechnology company developing imipridones, a novel class of compounds (Press release, Oncoceutics, JAN 8, 2021, View Source [SID1234651247]). Oncoceutics’ lead product candidate, ONC201, has been shown in clinical testing to selectively induce cell death in multiple cancer types. ONC201 is currently in a registrational clinical trial for recurrent H3 K27M-mutant glioma and a confirmatory response rate assessment is expected in 2021.

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!

ONC201 is an orally administered small molecule dopamine receptor D2 (DRD2) antagonist and caseinolytic protease (ClpP) agonist in late-stage clinical development for recurrent gliomas that harbor the H3 K27M mutation. Recurrent glioma is a form of brain cancer with a particularly poor prognosis having a median overall survival of approximately eight months. Recurrent pediatric patients, with cancer that carries the H3 K27M mutation, have an even worse prognosis with median overall survival of approximately four months. Compelling responses at this stage of disease are rare and lack durability. Patients with this mutation are considered grade IV by the World Health Organization, regardless of underlying histology or age. Initial evaluation of data from the full 50-subject registration cohort, which remains subject to full maturation and confirmation by Blinded Independent Central Review (BICR), indicate a compelling and particularly durable single agent Overall Response Rate (ORR) of at least 20% as assessed by Response Assessment in Neuro-Oncology-High Grade Glioma (RANO-HGG). The final confirmatory data analysis is expected in 2021.

"Patients with H3 K27M-mutant glioma are in desperate need of better therapeutic alternatives," said Dr. Patrick Wen, Director, Center for Neuro-Oncology at the Dana-Farber Cancer Institute and professor of Neurology at Harvard Medical School. "The tumor responses and safety profile we have observed with ONC201 in this devastating disease are compelling and I look forward to the possibility of accelerating its delivery to patients."

"Glioma remains one of the highest areas of unmet need in oncology where even first-line radiation therapy, as well as temozolomide in eligible patients, is not meaningfully effective and subsequent therapies are considered palliative. Further, there are no molecularly-targeted therapies for patients which harbor the H3 K27M mutation in this life-limiting disease. Given the urgent need and based on discussions with the FDA, there is a potential accelerated path to approval based on overall response. With a registration cohort of patients fully enrolled, treated, and preliminary data in hand, ONC201 offers an exciting near-term opportunity to quickly bring a potentially life-saving therapy and hope to patients with limited or no options," said Mike Sherman, Chief Executive Officer of Chimerix. "Our team is uniquely positioned to advance ONC201 given our considerable experience bringing targeted oncology products through the regulatory process."

"Oncoceutics represents a transformative acquisition for Chimerix, positioning the company with five assets across all stages of development and delivering on our goal to focus on oncology opportunities, complementing our Phase 3 study in acute myeloid leukemia with DSTAT.

With the upcoming Prescription Drug User Fee Act (PDUFA) date of April 7, 2021 for brincidofovir in smallpox and the confirmatory response rate assessment of ONC201 in 2021, we expect these near-term milestones to accelerate delivery of two new therapies in areas of particularly high unmet need," concluded Mr. Sherman.

"We are thrilled to join the Chimerix team to help accelerate ONC201 to glioma patients in urgent need of effective treatments. Chimerix has the leadership and resources to bring this program successfully through to approval and to further develop other promising assets in the Oncoceutics pipeline," said Lee Schalop, M.D., Chief Executive Officer of Oncoceutics. "This acquisition builds upon the vision of my co-founder Wolfgang Oster, M.D., Ph.D., scientific founder Wafik El-Deiry, M.D., Ph.D., FACP and all the employees at Oncoceutics in developing a therapy for patients for which there is no available treatment."

Clinical Development Plan for ONC201 in H3 K27M-mutant Glioma

The current Phase 2 clinical program for ONC201 includes a 50 subject registration cohort comprised of patients greater than 2 years of age with recurrent diffuse midline glioma that harbor the H3 K27M mutation, that have measurable disease, received radiation at least 90 days prior to enrollment and displayed evidence of progressive disease, and certain other criteria. This registration cohort is comprised of patients from multiple clinical trials and has completed enrollment. A BICR analysis is expected to take place in 2021 which, if favorable, may form the basis for regulatory approval of ONC201 in the United States. A BICR of the first 30 patients was completed and presented at the Society of Neuro-Oncology meeting held in November 2020. ONC201 has demonstrated a favorable safety profile with a database of over 350 treated patients. ONC201 has been generally well tolerated during extended periods of administration and the most commonly reported adverse events (AEs) were nausea/vomiting, fatigue and decreased lymphocyte counts.

The FDA has granted ONC201 Fast Track Designation for the treatment of adult recurrent H3 K27M-mutant high-grade glioma, Rare Pediatric Disease Designation for treatment of H3 K27M-mutant glioma, and Orphan Drug Designations for the treatment of glioblastoma and for the treatment of malignant glioma.

Over 300 subjects with recurrent high-grade gliomas, including gliomas with H3 K27M mutations, have been treated with ONC201 across three company-sponsored studies and an expanded access program.

Transaction Terms

Under the terms of the acquisition, Chimerix will pay Oncoceutics shareholders $78 million, of which $39 million is payable in Chimerix stock and $39 million is payable in cash, subject to certain customary adjustments. The payment of $39 million in cash is split $25 million at closing and $14 million on the first anniversary of closing. Oncoceutics shareholders will also potentially earn development, regulatory and sales milestones totaling up to $360 million across three development programs and royalties on combined sales of ONC201 and ONC206 of 15% up to $750 million in annual revenue and 20% above $750 million in annual revenue.

The Boards of Directors of both companies have approved the transaction and the transaction closed simultaneously with execution of definitive agreements on January 7, 2021.

Cooley LLP served as legal advisor to Chimerix. Evercore and Morgan Lewis served as exclusive financial advisor and legal advisor, respectively, to Oncoceutics. Spring Mountain Capital is the lead Oncoceutics investor.

Conference Call and Webcast

Chimerix will host a conference call and live audio webcast today at 8:30 a.m. ET. Slides that support the conference call are available in the Investors section of the Chimerix website, www.chimerix.com. To access the live conference call, please dial 877-354-4056 (domestic) or 678-809-1043 (international) at least five minutes prior to the start time and refer to conference ID 1877809.

A live audio webcast of the call will also be available on the Investors section of Chimerix’s website, www.chimerix.com. An archived webcast will be available on the Chimerix website approximately two hours after the event.

On January 8, 2021 Blacksmith Medicines, Inc. (Blacksmith), a biotechnology company focused on creating novel medicines for immuno-oncology and inflammatory diseases by targeting human metalloenzymes, reported that it has secured seed funding and has entered into a research collaboration with Eli Lilly and Company (Lilly) (Press release, Blacksmith Medicines, JAN 8, 2021, View Source [SID1234643541]). Lilly joins existing Blacksmith investors Evotec A.G., MP Healthcare Partners, MagnaSci Ventures, and Alexandria Venture Investments. Blacksmith is a spin-out of Forge Therapeutics, a leading antibiotic discovery company discovering therapies to combat the rise of drug resistance.

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 terms of the research collaboration agreement, Blacksmith and Lilly will collaborate on up to 5 human metalloenzyme targets, with Blacksmith advancing novel small molecule inhibitors from fragment to ‘hit’ stage after which Lilly has the right to continue research, development, and commercialization. Blacksmith will receive an upfront payment and an investment from Lilly in exchange for a convertible note and will be eligible for up to approximately $60 million per target in potential research, development and commercial milestones for a total potential deal size up to approximately $300 million.

The Blacksmith metalloenzyme platform is a unique drug discovery engine purpose-built to target the largest and most diverse group of enzymes in the human genome. Blacksmith’s proprietary platform has several distinct advantages over traditional drug discovery approaches including:

A large proprietary fragment library of metal-binding pharmacophores (MBPs);
A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.
"We are excited to launch Blacksmith Medicines with our investors and enter this research collaboration with Lilly, who collectively share our commitment to advancing novel chemistry approaches to create new medicines for patients in need," said Zachary Zimmerman, Ph.D., CEO and co-founder. "With the creation of Blacksmith, we are now able to expand our metalloenzyme platform into other therapeutic areas outside of anti-infectives, deepening our expertise and creating increased value for our shareholders, strategic partners and patients. We look forward to broadening the reach of our technology as we focus our efforts on identifying novel targets for immuno-oncology and inflammatory diseases."

On January 8, 2021 HLB reported that its Chinese partner, Jiangsu Hengrui Medicine, has received marketing approval for its Rivoceranib, locally branded as Apatinib, as a second-line treatment for liver cancer from the China National Medical Products Administration (Press release, HLB, JAN 8, 2021, View Source [SID1234591437]).

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 company expects Rivoceranib to expand its market share in China with the recent authorization, following the approval as a third-line treatment for gastric cancer in 2014.

HLB’s Chinese partner, Jiangsu Hengrui Medicine, has recently received marketing approval for Rivoceranib as a second-line treatment for liver cancer from the China National Medical Products Administration. (HLB)
Liver cancer is the second most common malignancy in China following lung cancer, and more than half of all liver cancer patients in the world are Chinese.

Jiangsu Hengrui Medicine launched Rivoceranib as a third-line treatment for gastric cancer with the name Aitan in China previously, and it has been receiving health insurance benefits since.

Aitan’s sales steadily increased from about 55 billion won ($50.3 million) in 2015, the first year of launching, to 350 billion in 2019.

HLB is conducting a global phase 3 clinical trial of combination therapy of Rivoceranib and Camrelizumab, an anticancer drug developed by Jiangsu Hengrui Medicine, targeting the first-line liver cancer treatment.

The company has almost completed recruiting patients for the clinical studies, and it plans to commercialize Rivoceranib by receiving indications for gastric and liver cancer and adenocystic carcinoma.

Under the accord, HLB will receive royalties as Jiangsu Hengrui Medicine start marketing Rivoceranib. The latter performs phase 3 studies of Rivoceranib for treating breast, non-small cell lung, and ovarian cancer.

"Rivoceranib has won marketing approval in China as a treatment for liver cancer following after stomach cancer, proving its value and expandability as a new anticancer drug," an official of HLB said. "We will focus on clinical trials to expand indications and do our best to realize direct selling in addition to the royalty received."