On March 18, 2021 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat specialty cancers and urologic diseases, reported that the Company has entered into a strategic funding agreement with RTW Investments, LP and its affiliated entities ("RTW") (Press release, UroGen Pharma, MAR 18, 2021, View Source [SID1234576881]).

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 agreement, subject to customary closing conditions, UroGen will receive $75 million in upfront cash from RTW in return for tiered, future cash payments based on aggregate worldwide annual net product sales of Jelmyto (mitomycin) for pyelocalyceal solution as well as UGN-102, if approved. In exchange for the $75 million upfront payment, RTW will receive tiered, future cash payments on worldwide annual net product sales of Jelmyto ranging from high to low single digits based on certain annual sales thresholds, subject to upward adjustment if certain annual sales and regulatory milestones are not met. RTW will also receive tiered, future cash payments on worldwide annual net product sales of UGN-102, if approved, in the low single digits based on certain annual sales thresholds.

The future payments on both Jelmyto and UGN-102 will terminate following the date that RTW has received an aggregate amount pursuant to such payments of $300 million.

"UroGen’s RTGel platform has demonstrated the ability to overcome historical treatment barriers, work with anatomical complexity and thus unlock new therapeutic potential, including those conditions targeted by Jelmyto and UGN-102," said Brad Sitko, Managing Director of Strategic Finance, RTW Investments, LP. "We are proud to partner with the UroGen management team and look forward to supporting the Company’s goal of building a leading uro-oncology company."

"This important non-dilutive transaction provides a clear path to fund the ongoing launch of Jelmyto and to advance our UGN-102 program, including the ongoing Phase 3 ATLAS study," said Molly Henderson, Chief Financial Officer of UroGen Pharma. "We are proud to partner with RTW, a leading, research-driven healthcare investor, allowing us to access capital that is aligned with our vision and invest further in our mission of developing treatments for patients with urologic and specialty cancers."

Cowen acted as financial advisor to UroGen on the transaction. Cooley acted as legal advisor to UroGen. Gibson Dunn acted as legal advisor to RTW.

On March 18, 2021 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported its fourth quarter and full year 2020 financial results, and provided recent corporate and program highlights (Press release, Aeglea BioTherapeutics, MAR 18, 2021, View Source [SID1234576843]).

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!

"2020 was a challenging year advancing our clinical trials and at the same time prioritizing the health and well-being of the rare disease patients we serve, who often have additional difficulties and vulnerabilities," said Anthony Quinn, M.B Ch.B, Ph.D., president and chief executive officer of Aeglea. "We have been focused on mitigating the impact of COVID-19 on our clinical timelines and I’m proud of the work the team has done to put patient needs first while also advancing a broad range of other impactful activities, as seen with the regulatory designations received for AGLE-177, our continuous gains in Arginase 1 Deficiency patient identification and the buildout of our commercial organization."

Dr. Quinn continued, "With enrollment completion expected this month and data expected in the fourth quarter for our pivotal Phase 3 PEACE study of pegzilarginase in Arginase 1 Deficiency, and the potential for first-in-human data from our AGLE-177 Phase 1/2 clinical trial in Homocystinuria, 2021 is shaping up to be a transformational year and we are well positioned to evolve into a successful commercial-stage company."

Recent Highlights and Updates

Pegzilarginase in Arginase 1 Deficiency

As of mid-March, 24 patients have been enrolled and randomized in the pivotal Phase 3 PEACE clinical trial. An additional nine patients are in active screening or scheduled to begin screening in the next two weeks. Trial enrollment is expected to close in March, with completion of screening and all patients randomized by the end of April. Topline data is expected in the fourth quarter of 2021.
As of January, Aeglea has identified over 300 Arginase 1 Deficiency patients in addressable markets. The number of currently identified patients represents approximately 65% and 30% of the estimated genetic prevalence populations in the U.S. and EU4 plus the UK, respectively.
At the 2021 JP Morgan Healthcare Conference, Aeglea provided an update on the safety profile of pegzilarginase. As of September 2020, more than 1,350 doses had been administered in the Phase 1/2 clinical trial and Phase 2 open-label extension study.
AGLE-177 in Homocystinuria

In December 2020, Aeglea announced the U.S. Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation to AGLE-177 for the treatment of Homocystinuria. If AGLE-177 is approved by the FDA, the company will be eligible to receive a Priority Review Voucher.
In January, Aeglea announced it will be adding clinical trial sites in Australia for its Phase 1/2 clinical trial.
In January, the Company presented the results of an analysis which determined the Classical Homocystinuria (CBS deficiency) population in global addressable markets may exceed 30,000 patients, with an estimated 15,000-18,000 of those patients to be non-responsive to the existing standard of care.
Corporate

Aeglea expanded the Company’s Board of Directors to include two new members. Alison Lawton, who previously served as president and CEO of Kaleido Biosciences, was appointed in December 2020. Sara Brownstein, a principal at Baker Bros. Advisors LP, was appointed in February 2021.
Upcoming Events

Aeglea will be attending the following virtual investor conferences:

Wells Fargo Annual Biotech Corporate Access Day, April 6
20th Annual Needham Healthcare Conference, April 12-13
Fourth Quarter and Full Year 2020 Financial Results

As of December 31, 2020, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $148.1 million. Based on Aeglea’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2023.

Research and development expenses totaled $15.8 million for the fourth quarter of 2020 and $17.6 million for the fourth quarter of 2019. The decrease was primarily associated with completing certain manufacturing and pre-commercial activities for Aeglea’s lead product candidate, pegzilarginase.

Research and development expenses totaled $59.6 million for the year ended December 31, 2020 and $64.6 million for the year ended December 31, 2019. The decrease was primarily associated with completing a Phase 1/2 clinical trial in patients with Arginase 1 Deficiency and closing cancer related trials, completing certain manufacturing and pre-commercial activities for Aeglea’s lead product candidate, pegzilarginase, along with supporting toxicology studies for the Homocystinuria program.

General and administrative expenses totaled $7.0 million for the fourth quarter of 2020 and $4.3 million for the fourth quarter of 2019. This increase was primarily due to ramping-up commercial capabilities and infrastructure.

General and administrative expenses totaled $21.8 million for the year ended December 31, 2020 and $15.7 million for the year ended December 31, 2019. This increase was primarily due to ramping-up commercial capabilities and infrastructure along with additional office space to support company growth.

Net loss totaled $22.7 million and $21.5 million for the fourth quarter of 2020 and 2019, respectively, with non-cash stock compensation expense of $1.6 million and $1.2 million for the fourth quarter of 2020 and 2019, respectively. Net loss totaled $80.9 million and $78.3 million for the years ended December 31, 2020 and 2019, respectively, with non-cash stock compensation expense of $6.3 million and $4.9 million for the years ended December 31, 2020 and 2019, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme, which has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of patients with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality. Aeglea’s Phase 1/2 and Phase 2 open-label extension data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. The Company’s ongoing single, global pivotal Phase 3 PEACE trial is designed to assess the effects of treatment with pegzilarginase versus placebo over 24 weeks with a primary endpoint of plasma arginine reduction. Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough, Fast Track and Orphan Drug Designations from the FDA as well as Orphan Drug Designation from the European Medicines Agency.

About AGLE-177 in Homocystinuria

AGLE-177 is a novel recombinant human enzyme, which degrades the amino acid homocysteine and its related homocystine dimer. Aeglea is developing AGLE-177 for the treatment of patients with cystathionine beta synthase (CBS) deficiency, also known as Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of homocysteine and homocystine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received U.S. Rare Pediatric Disease and Orphan Drug Designations as well as EU Orphan Drug Designation. Aeglea initiated a Phase 1/2 trial in the second quarter of 2020 and continues patient identification and administrative activities.

On March 18, 2021 Debiopharm (www.debiopharm.com), a Swiss-based global biopharmaceutical company, reported the signature of an exclusive license agreement with Merck KGaA, Darmstadt, Germany , a leading science and technology company, for the development and commercialization of xevinapant (Debio 1143) (Press release, Debiopharm, MAR 18, 2021, View Source [SID1234576866]). Xevinapant, a potent, oral of Inhibitor of Apoptosis Proteins (IAP) antagonist, is the only medicine in its class in late-stage clinical development and has the potential to be first in class. Xevinapant is currently being investigated in the pivotal Phase III TrilynX study for previously untreated high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), in combination with platinum-based chemotherapy and standard fractionation intensity-modulated radiotherapy. Given their strong commercial footprint in the field of head and neck cancer, Merck KGaA, Darmstadt, Germany is the partner of choice to leverage our outstanding phase II data and make xevinapant a transformative therapy for cancer patients.

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 license agreement, Merck KGaA, Darmstadt, Germany receives exclusive rights to develop and commercialize xevinapant worldwide, including in the U.S. Merck KGaA, Darmstadt, Germany will also co-fund with Debiopharm the ongoing Phase III registrational TrilynX study, a global double-blind, placebo-controlled, 700-patient randomized clinical trial to evaluate the efficacy and safety of xevinapant vs. placebo when added to definitive chemoradiotherapy (CRT) in cisplatin-eligible patients with high-risk LA SCCHN.

This global license agreement is a significant achievement that rewards the clinical development efforts conducted by Debiopharm while demonstrating the agility and relevance of the company’s specific and unique business model. By focusing on drug development, Debiopharm can bridge the most innovative discoveries with the best commercial pharmaceutical partners.

"At Debiopharm we are driven by the ambition to cure. Our business model is led by the needs of patients and unmet medical needs. The data for xevinapant to date demonstrate an extremely important potential to improve the standard treatment for patients with head and neck cancer, an indication for which no new treatment has been registered for several decades, Merck KGaA, Darmstadt, Germany’s in-depth knowledge of head and neck cancer and their worldwide commercial capabilities, make them an exceptionally qualified partner to move xevinapant forward, and position it as the next gold standard of care in head and neck cancer and potentially in other indications."
– Bertrand Ducrey, Chief Executive Officer of Debiopharm.

"By bringing our expertise and heritage in head and neck cancer to the development of xevinapant, we have the opportunity to explore an important new treatment option in an area of high unmet need where other approaches, including immunotherapy, have seen limited success, The promising long-term efficacy of xevinapant in the Phase II clinical study suggests that antagonism of IAP has the potential to be a transformative approach in this cancer. We will build on this strong proof of concept, shown in Debiopharm’s robust clinical program for xevinapant, as we continue to develop this potential new standard of care."
– Peter Guenter, Member of the Executive Board of Merck KGaA, Darmstadt, Germany and CEO Healthcare

"Locally advanced head and neck cancer is uniquely debilitating, often impairing the ability to swallow, speak and breathe. With the current standard treatments, at least half of patients will relapse, typically within the first two years. Based on the efficacy seen in the Phase II study, in which adding xevinapant to CRT cut the risk of death by half, this investigational medicine has the potential to offer a much-needed new standard of care."
– Prof. Jean Bourhis, Department Head of Radio-Oncology at the University Hospital of Lausanne and lead investigator of the Phase III TrilynX study.

Previously reported results from the randomized, double-blind Phase II clinical study showed the addition of xevinapant to standard-of-care CRT provided a statistically significant 21% point improvement in locoregional control rate at 18 months, the primary endpoint, vs. placebo and CRT in patients with high-risk LA SCCHN (54% [95% CI: 39 to 69] vs. 33% [95% CI: 20 to 48]; odds ratio 2·69 [95% CI: 1·13 to 6·42]; p=0·026). A significant progression-free survival (PFS) benefit was also observed vs. the control arm after a two-year follow-up period (HR=0.37, 95% CI: 0.18 to 0.76; p=0.0069). At three years of follow-up, xevinapant plus CRT showed a statistically significant 51% reduction in the risk of death versus placebo plus CRT (HR=0.49, 95% CI: 0.26 to 0.92; p=0.0261). About two-thirds of patients in the xevinapant arm were alive at three years, compared with 51% in the control arm.

In February 2020, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to xevinapant for treatment of patients with confirmed diagnosis of previously untreated LA SCCHN in combination with current standard of care, platinum-based chemotherapy and standard-fractionation intensity-modulated radiotherapy, based on the Phase II results.

About Head and Neck Cancer
Worldwide, head and neck cancer accounts for more than 650,000 cases and 330,000 deaths annually, making it the 6th most common cancer type. LA SCCHN is a highly debilitating disease that can lead to impaired breathing, swallowing, and speech as it progresses. Despite standard of care CRT, at least 40% to 60% of patients with LA SCCHN develop locoregional or distant relapses, which are usually detected within the first two years of treatment, underscoring the need to identify new therapeutic approaches.

About xevinapant
Xevinapant (Debio 1143) is a potential first-in-class potent oral antagonist of IAPs (Inhibitor of Apoptosis Proteins). In preclinical studies, xevinapant restores sensitivity to apoptosis in cancer cells, thereby depriving them of one of their major resistance mechanisms. As the most clinically advanced IAP antagonist, xevinapant has established proof of efficacy in combination with chemoradiotherapy (CRT) in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), with a clinically significant and sustained clinical benefit compared with CRT alone.

Debiopharm’s commitment to patients
Debiopharm develops innovative therapies that target high unmet medical needs in oncology and infectious diseases. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy and then select large pharmaceutical commercialization partners to maximize patient access globally. Debiopharm is known for the development of oxaliplatin, worldwide gold standard treatment in colorectal cancer and of triptorelin, a standard of care for the treatment of prostate cancer. Xevinapant is well positioned to become the third transformative therapy arising from Debiopharm in oncology.

On March 18, 2021 Xcovery Holdings, Inc., an oncology focused bio-pharmaceutical company, reported that Giovanni Selvaggi, M.D., has been appointed as the Chief Executive Officer (CEO), replacing Li Mao, M.D., who is leaving for personal reasons (Press release, Xcovery, MAR 18, 2021, View Source [SID1234576882]). Dr. Selvaggi will also continue as Xcovery’s Chief Medical Officer (CMO).

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!

"Giovanni is the right leader for Xcovery," said Lieming Ding, M.D., Chairman of the Board. "For the past two years, Giovanni has been successfully driving forward the ensartinib and vorolanib clinical programs as the company CMO. His proven leadership and industry expertise will be crucial for the regulatory and commercial success of our drugs."

"Xcovery is at a critical yet very exciting juncture," stated Dr. Selvaggi. "I’m ready to take on the new challenges and responsibilities. We have a very good late stage clinical program in ensartinib, which has the potential to be the best-in-class treatment for ALK+ NSCLC patients. We are taking the drug over the finish line so NSCLC patients can have a new option to fight the disease."

Dr. Selvaggi received his medical degree at the University of Torino Medical School in 1992 and served as physician of Thoracic Oncology in Torino over a span of 16 years. Dr. Selvaggi joined the pharmaceutical industry in 2010 as a medical director at GlaxoSmithKline. He then played an instrumental role in the successful development and registration of ceritinib (Zykadia) at Novartis. Dr. Selvaggi was also at Bristol-Myers Squibb as Program Lead in different thoracic malignancies with a focus on SCLC. From March 2019, Dr. Selvaggi has been the Chief Medical Officer at Xcovery.

On March 18, 2021 Boston Scientific Corporation (NYSE: BSX) reported it has received U.S. Food and Drug Administration (FDA) approval of the TheraSphere Y-90 Glass Microspheres, developed for the treatment of patients with hepatocellular carcinoma (HCC) (Press release, Boston Scientific, MAR 18, 2021, View Source [SID1234576844]). The approval expands access to this life-prolonging therapy for a greater number of patients, which, to date, has been utilized under a humanitarian device exemption (HDE) – an FDA classification which required institutional review board approval and limited the number of patients treated with the therapy per year. TheraSphere is now the only radioembolization technology indicated for the treatment of unresectable HCC in the U.S.

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!

HCC is one of the most prevalent cancers in the world and the most common type of primary liver cancer, with more than half a million new global cases diagnosed annually.i The American Cancer Society estimates that approximately 32,000 new cases of HCC will be diagnosed in the U.S. in 2021.ii It is most often treated through surgery, liver transplantation, chemotherapy or embolization, including both chemoembolization and radioembolization – also commonly referred to as selective internal radiation therapy (SIRT). TheraSphere treatment, a type of SIRT with low toxicity, is comprised of millions of microscopic glass beads containing radioactive yttrium (Y-90), which are delivered directly to liver tumors via catheter and result in minimal exposure to surrounding healthy tissue.

TheraSphere-Vial-and-Sphere

TheraSphere-Vial-and-Sphere
Approval of TheraSphere was based on results from the LEGACY study, designed to evaluate the safety and efficacy of the therapy for the treatment of early and advanced HCC. The study analyzed data from 162 patients and met both primary endpoints of objective response rate and duration of response rate (72.2% at four weeks and 76.1% at six months, respectively).iii, iv,v,vi Data demonstrated 100% complete or partial patient response up to two TheraSphere treatments – disappearance of all lesions or >/= 30% decrease in target lesion diameter – and a 93% overall survival rate in patients with transplant or resection following treatment at three years.

"I am honored to have spearheaded the LEGACY trial in which we found that patients with early and advanced HCC exhibited very high response rates as well as clinically meaningful durations of response and survival, establishing TheraSphere as a standard treatment for this patient population," said Riad Salem, M.D., M.B.A, interventional radiologist at Northwestern Memorial Hospital and principal investigator of the LEGACY trial. "The trial results, which have been accepted for publication in Hepatology, produced one of the most comprehensive databases for TheraSphere, empowering physicians to make informed, data-driven decisions for their patients."

Treatment with TheraSphere does not require hospitalization and is typically performed as an outpatient procedure in as little as an hour, potentially alleviating pressure on healthcare systems in an increasingly complex care environment. Recognition of the benefits of SIRT – both to patients and hospitals – were reflected in recently issued guidance from the National Institute for Health and Care Excellence (NICE) when they recommended the use of TheraSphere for the treatment of patients with HCC through the National Health Service (NHS) in England, Wales and Northern Ireland.

"The FDA approval and the recent NICE recommendation will expand access to TheraSphere, which has demonstrated improvement in both survivability and quality of life through 20 years of clinical trials and real-world outcomes in the more than 70,000 patients globally," said Peter Pattison, president of Interventional Oncology, Peripheral Interventions, Boston Scientific. "We expect to continue to focus our efforts on bringing this treatment to more patients, both by planning a randomized trial to study the combination of TheraSphere and immunotherapy in patients with HCC not eligible for curative treatments, as well as further investigating the therapy for different cancer segments, including prostate and brain."