On August 25, 2021 Eli Lilly and Company (NYSE: LLY) and Lycia Therapeutics, Inc. reported a multi-year research collaboration and licensing agreement focused on the discovery, development and commercialization of novel targeted therapeutics using Lycia’s proprietary lysosomal targeting chimera, or LYTAC, protein degradation technology (Press release, Eli Lilly, AUG 25, 2021, View Source [SID1234586877]).

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Lycia uses its next-generation degradation approach to target the untapped extracellular proteome, including cell surface receptors and secreted proteins. The LYTAC platform may enable the development of several therapeutic modalities, including antibodies and small molecules, with the potential to inhibit many targets previously considered intractable across a spectrum of therapeutic areas and diseases.

Under the terms of the agreement, the companies will utilize Lycia’s LYTAC platform to discover and develop novel degraders for up to five targets that aim to address key unmet medical needs in Lilly’s therapeutic areas of focus, including immunology and pain. Lilly will be solely responsible for preclinical and clinical development of candidates and receives an exclusive worldwide license to commercialize potential medicines resulting from the agreement.

"This collaboration with Lycia furthers Lilly’s strategy to utilize innovative new technology to treat challenging disease areas, such as immunology and pain," said Ajay Nirula, M.D., Ph.D., vice president of immunology at Lilly. "We believe Lycia’s technology may allow us to develop targeted therapeutics that were not previously feasible and make advances for patients in areas of high unmet need."

"We are extremely pleased to establish this strategic collaboration with Lilly, a global leader in therapeutic innovation," said Aetna Wun Trombley, Ph.D., President and CEO of Lycia. "With our differentiated LYTAC platform for targeted extracellular protein degradation, we look forward to collaborating with Lilly to advance novel therapies against challenging targets in underserved disease areas while we simultaneously advance our in-house pipeline of first-in-class LYTAC-based therapeutics."

Lycia will receive an upfront payment of $35 million. The company is also eligible to receive over $1.6 billion in potential milestone payments based on the achievement of prespecified preclinical, development and commercial milestones, as well as tiered royalties from mid-single to low double-digits on sales resulting from the agreement.

This transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2021 non-GAAP earnings per share guidance as a result of this transaction.

On August 25, 2021 CTI BioPharma Corp. (Nasdaq: CTIC) (CTI) and DRI Healthcare Trust (TSX: DHT.UN) (TSX: DHT.U) (DRI) reported transactions totaling up to $135 million in funding for CTI, with $50 million in secured debt to be funded at closing and $60 million to purchase a tiered royalty on sales of pacrinitib upon product approval of pacrinitib by the U.S. Food and Drug Administration (FDA) (Press release, CTI BioPharma, AUG 25, 2021, View Source [SID1234586876]). The proceeds of the transactions will be used by CTI to fund the commercialization of pacritinib for the treatment of myelofibrosis patients with severe thrombocytopenia. CTI has a New Drug Application (NDA) under priority review by FDA with a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2021, and is preparing for a potential commercial launch by end of year.

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CTI BioPharma and DRI Healthcare Trust Announce up to $135 Million Debt and Royalty Transaction
"CTI is in a strong position to deliver a meaningful new treatment option for patients with myelofibrosis with thrombocytopenia who are in urgent need of new therapies. If we achieve our sales goals in the first two years of launch, we anticipate that this transaction will put us on a clear path to profitability," said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI Biopharma. "We thank DRI for their support of CTI and for their partnership during the launch and commercialization of pacritinib."

"We are excited to announce DRI’s partnership with CTI," said Behzad Khosrowshahi, Chief Executive Officer of DRI Healthcare Trust. "Pacritinib is a great addition to our portfolio as a new therapy that addresses a high unmet medical need for patients with myelofibrosis with severe thrombocytopenia."

"This transaction highlights our ability to offer flexible deal structures that provide DRI with excellent assets and strong cash flow, while providing for the objectives of our partners such as CTI," continued Mr. Khosrowshahi.

About the Transaction
DRI Healthcare will provide a $50 million credit facility at closing. The credit facility bears interest at LIBOR + 8.25% (with a LIBOR floor of 1.75%) and is interest-only for the loan term of 5 years, with the outstanding principal due at maturity. The company will be subject to one financial covenant, which is maintaining minimum liquidity of at least $10 million during the term of the loan.

DRI Healthcare will also provide CTI with $60 million upon receiving accelerated approval of pactritinib, and will receive royalties on annual pacrinitib net sales in the United States of 9.6% for the first $125 million of annual U.S. net sales, 4.5% between $125 million and $175 million of annual U.S. net sales, 0.5 % between $175 million and $400 million of annual U.S. net sales, with no entitlement above $400 million of annual U.S. net sales. CTI will be entitled up to an additional $25 million on achievement of certain sales milestones.

Cowen acted as financial advisor to CTI on this transaction.

About Myelofibrosis and Severe Thrombocytopenia
Myelofibrosis is bone marrow cancer that results in formation of fibrous scar tissue and can lead to severe thrombocytopenia and anemia, weakness, fatigue and enlarged spleen and liver. Patients with severe thrombocytopenia are estimated to make up more than one-third of patients treated for myelofibrosis, or approximately 17,000 people in the United States and Europe. Severe thrombocytopenia, defined as blood platelet counts of less than 50,000 per microliter, has been shown to result in overall survival rates of just 15 months. Thrombocytopenia in patients with myelofibrosis is associated with the underlying disease but has also been shown to correlate with treatment with ruxolitinib, which can lead to dose reductions, and as a result, may potentially reduce clinical benefit. Survival in patients who have discontinued ruxolitinib therapy is further compromised, with an average overall survival of seven to 14 months. Myelofibrosis patients with severe thrombocytopenia have limited treatment options, creating a significant area of unmet medical need.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, IRAK1, and CSF1R, but not JAK1. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia, and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL), due to its inhibition of c-fms, IRAK1, JAK2 and FLT.

On August 25, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported that it will host a virtual KOL event for analysts, investors, and the scientific community on Wednesday, September 8, 2021 (Press release, Cardiff Oncology, AUG 25, 2021, View Source [SID1234586875]).

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The webinar will include presentation of new data from Cardiff Oncology’s Phase 1b/2 clinical trial evaluating onvansertib in combination with standard-of-care FOLFIRI/bevacizumab in KRAS-mutated mCRC, featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP, USC Norris Comprehensive Cancer Center, key clinical advisor Afsaneh Barzi, M.D., Ph.D., City of Hope Comprehensive Cancer Center, and members of the Cardiff Oncology management team. A question & answer session will follow the formal presentations.

Heinz-Josef Lenz, M.D., FACP, is the associate director for clinical research and co-leader of the gastrointestinal (GI) cancers program at the University of Southern California Norris Comprehensive Cancer Center. Dr. Lenz is professor of medicine and preventive medicine, section head of gastrointestinal oncology in the division of medical oncology and co-director of the Colorectal Center at the Keck School of Medicine of the University of Southern California. Dr. Lenz received his medical degree from Johannes-Gutenberg Universität in Mainz, Germany, in 1985. He completed a residency in hematology and oncology at the University Hospital Tübingen in Germany, a clerkship in oncology at George Washington University in Washington, DC, and a clerkship in hematology at Beth Israel Hospital of Harvard Medical School in Boston, Massachusetts. He served subsequent fellowships in biochemistry and molecular biology at the University of Southern California Norris Comprehensive Cancer Center. An active researcher, Dr. Lenz focuses on topics including the regulation of gene expression involved in drug resistance, patients at high risk of developing colorectal cancer, and determination of carcinogenesis, methods of early detection, and better surveillance of these cancers. He is a member of several professional societies, including the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the American Gastroenterology Association, and the National Society of Genetic Counselors. He also serves on the National Advisory Board of several professional organizations. Dr. Lenz is the author of numerous peer-reviewed publications and invited papers, reviews, and editorials. He also serves as co-chair of the GI Committee and Correlative Science Committee for SWOG. He is a member of the National Cancer Institute (NCI) Task Force for Gastroesophageal Cancer, the NCI Steering Committee, and the NCI Translational Science Committee.

Afsaneh Barzi, M.D., Ph.D., is a practicing medical oncologist, associate clinical professor for gastrointestinal oncology, and clinical director of AccessHope at City of Hope Comprehensive Cancer Center. Prior to joining City of Hope, Dr. Barzi was an associate professor of clinical medicine at the Keck School of Medicine of the University of Southern California. She earned her M.D. from Tehran University of Medical Sciences, then went on to earn a Master’s in Health Informatics and a Doctorate in Public Health Management and Policy Sciences from the University of Texas Health Science Center in Houston. Dr. Barzi completed a fellowship in hematology and oncology at the Cleveland Clinic’s Taussig Cancer Center. Her research and practice are focused on gastrointestinal malignancies with an emphasis on colorectal cancers. Her unique perspective on patterns of care in patients with colorectal cancer arises from the combination of her expertise in real-world data and her experience with biomarker discovery and the use of biomarkers for personalized care.

On August 25, 2021 LianBio, a biotechnology company dedicated to bringing paradigm-shifting medicines to patients in China and other major Asian markets, and BridgeBio Pharma, Inc. (Nasdaq: BBIO) reported the first patient has been treated in a Phase 2a clinical trial of infigratinib in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with fibroblast growth factor receptor-2 (FGFR2) gene amplification and other advanced solid tumors with FGFR genomic alterations (Press release, BridgeBio, AUG 25, 2021, View Source [SID1234586874]).

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"Infigratinib is a potent and selective FGFR inhibitor that has demonstrated compelling clinical activity across multiple tumor types with FGFR alterations," said Yizhe Wang, Ph.D., chief executive officer of LianBio. "Given the disproportionately high prevalence rate of gastric cancer in China, LianBio is pursuing a region-specific development strategy focused on this area of great unmet need. This study marks LianBio’s first trial initiation and demonstrates our continued progress in delivering potentially transformational medicines to patients in Asia."

TRUSELTIQ (infigratinib) is an oral selective inhibitor of FGFR1-3 that is approved in the United States for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test. It is also being further evaluated in clinical trials based on demonstration of clinical activity in patients with advanced urothelial carcinoma with FGFR3 genomic alterations. LianBio in-licensed rights from BridgeBio for infigratinib for development and commercialization in Mainland China, Hong Kong and Macau.

The Phase 2a trial is a multicenter, open-label, single-arm study in China designed to evaluate the safety and efficacy of infigratinib in patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with FGFR2 gene amplification and other advanced solid tumors with FGFR alterations. The primary endpoint is objective response rate (ORR). Secondary endpoints include duration of response, safety, disease control rate, progression-free survival and overall survival.

Preclinical data have demonstrated the potential infigratinib may have for patients with gastric cancer. These results, published in Cancer Discovery, demonstrated tumor regression in multiple in vivo FGFR2 amplified gastric models.1

"We believe that infigratinib could have a meaningful impact for people living with gastric cancer as well as many other cancers with FGFR alterations, and are pleased LianBio is initiating this clinical trial in China where more therapeutic options are needed to match the growing diagnosis rate," said BridgeBio founder and chief executive officer Neil Kumar, Ph.D. "On the heels of TRUSELTIQ recently obtaining accelerated approval in the United States, we are hopeful that this trial will yield pivotal results in another subset of cancer patients as we continue to build our portfolio of oncology indications with the aim of reaching as many people in need as possible."

About TRUSELTIQ (infigratinib)

TRUSELTIQ (infigratinib) is an orally administered, ATP-competitive, tyrosine kinase inhibitor of fibroblast growth factor receptor (FGFR) that received accelerated approval from the FDA in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. TRUSELTIQ targets the FGFR protein, blocking downstream activity. In clinical studies, TRUSELTIQ demonstrated a clinically meaningful rate of tumor shrinkage (overall response rate) and duration of response. TRUSELTIQ is not FDA-approved for any other indication in the United States and is not approved for use by any other health authority, including any Chinese or other Asian health authority. It is currently being evaluated in clinical studies for first-line cholangiocarcinoma, urothelial carcinoma (bladder cancer), locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma, and other advanced solid tumors with FGFR genomic alterations.

On August 25, 2021 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to potentially create new treatments that make a meaningful difference in patients’ lives, reported financial results for the second quarter ended June 30, 2021 (Press release, Ascendis Pharma, AUG 25, 2021, View Source [SID1234586873]).

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"We are actively preparing for the U.S. commercial launch of SKYTROFA for the treatment of children with GHD, which is now the first FDA-approved once-weekly treatment for pediatric GHD. SKTROFA is also the first FDA-approved product utilizing our innovative TransCon technology. Our pivotal heiGHt Trial demonstrated that once-weekly TransCon hGH increased annualized height velocity in treatment-naïve subjects at 52 weeks compared to a daily growth hormone with comparable safety and tolerability," said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. "We see this approval as the first step in creating a market leading product and building a fully integrated global biopharmaceutical company guided by our values of patients, science, and passion."

Company Highlights & Progress

TransCon hGH (lonapegsomatropin)
TransCon hGH is now FDA approved in the U.S. under the brand name SKYTROFA. Continued preparation for commercial launch for the treatment of pediatric patients with GHD in the U.S.
European Commission decision on the company’s Marketing Authorisation Application (MAA) for the treatment of pediatric patients with GHD is anticipated in the fourth quarter of 2021.
Ongoing enrollment in the foresiGHt Trial, a global phase 3 trial in adults with GHD, and the riGHt Trial, a phase 3 trial in Japan in pediatric patients with GHD.
Patient follow-up continues in enliGHten, a multi-center phase 3, long-term open-label trial investigating safety and efficacy of SKYTROFA in pediatric patients with GHD.
Comprehensive results from the heiGHt Trial recently published on-line in the Journal of Clinical Endocrinology & Metabolism, an official journal of the Endocrine Society.
TransCon PTH (palopegteriparatide)
Exceeded target enrollment in the PaTHway Trial, a phase 3 trial evaluating the safety, tolerability, and efficacy of palopegteriparatide in adult subjects with hypoparathyroidism with similar demographics as enrolled in the phase 2 trial including broad representation of different non-surgical disease etiologies and leading influential clinical sites balanced between North America and Europe.
On track to announce 84-week top line results from the open label extension (OLE) portion of the PaTH Forward Trial in the fourth quarter of 2021. Continued strong long-term subject retention with 58 out of the 59 randomized subjects continuing in the OLE portion of the trial as of August 23, 2021.
Clinical trial notification for the PaTHway Japan Trial was accepted by the Japanese Pharmaceuticals and Medical Device Agency. The single-arm, phase 3 study will enroll a minimum of 12 Japanese subjects with HP.
Received Orphan Drug Designation (ODD) from the Japanese Ministry of Health, Labor and Welfare.
VISEN Pharmaceuticals (VISEN) obtained investigational new drug (IND) approval to initiate the phase 3 PaTHway China Trial.
TransCon CNP
Continued execution in the ongoing phase 2 ACcomplisH Trial and ACcomplisH China Trial to evaluate the safety and efficacy of TransCon CNP in children ages two to ten years with achondroplasia.
Clinical program update planned for the fourth quarter of 2021.
TransCon TLR7/8 Agonist
Initiated combination therapy arm in transcendIT-101 with TLR7/8 Agonist and a CPI.
TransCon IL-2 ß/y
IND filing on track for this quarter.
Ended the second quarter of 2021 with cash, cash equivalents and marketable securities totaling €641.3 million.
Second Quarter 2021 Financial Results

For the second quarter, Ascendis Pharma reported a net loss of €134.4 million, or €2.50 per share (basic and diluted) compared to a net loss of €94.9 million, or €1.97 per share (basic and diluted) for the same period in 2020.

Revenue for the second quarter was €1.0 million compared to €1.4 million in the same quarter of 2020. The decrease was due to a lower amount of license revenue being recognized, partly offset by higher sale of clinical supplies and services to VISEN and recognition of revenue from services rendered to another collaboration partner.

Research and development (R&D) costs for the second quarter were €83.3 million compared to €63.6 million during the same period in 2020. Higher R&D costs in 2021 reflect an increase in external development costs of the company’s product candidates and an increase in personnel-related costs.

Selling, general and administrative expenses for the second quarter were €35.3 million compared to €20.8 million during the same period in 2020. The increase is primarily due to higher personnel-related costs and an increase in IT costs.

Net loss of associate for the second quarter was €4.8 million compared to a net loss of €1.9 million in the same quarter of 2020. The net loss of associate represents our share of the net result from VISEN.

As of June 30, 2021, Ascendis Pharma had cash, cash equivalents and marketable securities of €641.3 million compared to €771.1 million as of March 31, 2021. As of June 30, 2021, Ascendis Pharma had 53,900,990 ordinary shares outstanding.

Conference Call Details

A live webcast of the conference call will be available on the Investors and News section of the Ascendis Pharma website at www.ascendispharma.com. A webcast replay will be available on this website shortly after conclusion of the event for 30 days.

About Ascendis Pharma’s Pipeline

Ascendis Pharma currently has three product candidates in clinical development in rare endocrine diseases and one oncology product candidate in clinical development:

TransCon hGH (lonapegsomatropin-tcgd), an investigational long-acting prodrug of somatropin (human growth hormone or hGH) that releases somatropin with the identical amino acid sequence and size as daily growth hormone, is designed as a once-weekly treatment for GHD and is approved for pediatric GHD by the U.S. Food and Drug Administration and under review by the European Medicines Agency.
TransCon PTH (palopegteriparatide), an investigational long-acting prodrug of parathyroid hormone (PTH) in phase 3 development as a once-daily replacement therapy for adults with hypoparathyroidism designed to replace PTH at physiologic levels for 24 hours, and address both short-term symptoms and long-term complications of the disease.
TransCon CNP, an investigational long-acting prodrug of C-type natriuretic peptide (CNP) in phase 2 development as a therapy for children with achondroplasia (ACH), the most common form of dwarfism, for which there is no FDA-approved treatment. TransCon CNP is designed to provide continuous exposure of CNP at safe, therapeutic levels via a single, weekly subcutaneous dose.
TransCon TLR7/8 Agonist is an investigational long-acting prodrug of resiquimod, a small molecule agonist of Toll-like receptors (TLR) 7 and 8. Administered as an intratumoral injection, TransCon TLR7/8 Agonist is designed to provide sustained activation of intratumoral antigen presenting cells driving tumor antigen presentation and induction of immune stimulatory cytokines in the tumor.
TransCon IL-2 ß/y is an investigational long-acting prodrug of IL-2 ß/y designed for optimized IL-2R ß/y bias and potency, combined with low Cmax and long exposure.