On March 18, 2021 Swedish-based Newbury Pharmaceuticals AB, a hybrid pharmaceutical company for specialty prescription drugs, innovation and brands, has successfully completed its Series A funding round of 25 MSEK (Press release, Newbury Pharmaceuticals, MAR 18, 2021, View Source [SID1234632241]).

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The oversubscribed Series A financing brings 25 MSEK from selected strategic investors. Proceeds from the funding round will support to continue building a pipeline of proprietary and licensed products. The portfolio strategy includes niche and value-added small molecules, product development based on peptide technology as well as biosimilars in a variety of therapeutic categories.

"We have the ambition to become the local champion and alternative partner to the multinationals. We strive to have a positive impact in the society, bring products and technology that contribute to the overall healthcare system and patient’s wellbeing – and give our partner the local attention they deserve" says Karl Karlsson, Founder & CEO.

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]).

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"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.

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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).

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"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 Xspray Pharma reported an update on the upcoming pivotal study with its improved version of Sprycel (dasatinib), based on the company’s HyNap-Dasa formulation (Press release, Xspray, MAR 18, 2021, View Source [SID1234650109]). The study has been initiated and the dosing for the bioequivalence study will start in the second quarter with the aim to submit an application for market approval in accordance with the 505(b)(2) procedure in the second half of 2021.

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In parallel with its development of generic protein kinase inhibitors (PKIs) based on the company’s amorphous technology platform, Xspray Pharma also develops improved versions of the original pharmaceutical agents. The overall strategy for HyNap-Dasa is unchanged and based on fastest possible route to market for;

a generic (ANDA) HyNap-Dasa version of Sprycel during the patent window
an improved (505(b)(2)) HyNap-Dasa version of Sprycel with relevant medical benefits
The improved version of Sprycel is designed to offer patients suffering from acute lymphocytic leukemia (ALL) and chronic myeloid leukemia (CML) an improved quality of life by enabling treatment with protein pump inhibitors, PPIs (omeprazole), together with the life-saving treatment with dasatinib. This improved version is also designed to overcome the issue with patients with low or no uptake as demonstrated for Sprycel in earlier bioequivalence studies. The improved version will also be administrated at a significantly lower strength compared to Sprycel and reduce variability. With these improvements HyNap-Dasa will offer meaningful medical benefits for patients and caregivers.

"Almost a third of the patient population has a need for PPIs. I hope that this improved version will offer them a treatment where you can treat cancer and for example ulcer at the same time. We will use the same formulation of HyNap-Dasa as was used in the bioequivalence studies that we ran in 2020 but giving a lower strength of HyNap-Dasa compared to Sprycel. Since we have already tested the formulation in healthy volunteers it is a de-risked study without significantly affecting our financial situation. We have a very robust set of pharmacokinetic data supporting the design of this study which reduces the risk considerably.", says Per Andersson, CEO Xspray Pharma.

The pivotal bioequivalence study aims to demonstrate that Xspray Pharma’s improved version can be administrated using significantly lower strength compared to the original drug and still obtain the same bioavailability. Previous studies with this formulation have already showed no food interaction and no drug-drug interaction with PPI, omeprazole.

"With our multiple pathway strategy, we are now in parallel developing both an improved and a generic version. Thereby we will be able to challenge the original product’s market position and create substantial value for the company and its shareholders. Our clinical work on the generic version of dasatinib continues according to plan. We are currently running a bioequivalence study with a slightly modified formulation and we expect data from this study in April. As a risk mitigating strategy, we are prepared to start studies with an additional formulation that has shown encouraging data in laboratory tests," concludes Per Andersson.

In 2020 Sprycel sold worldwide for USD 2,140 million of which USD 1,295 million was in the US. Xspray Pharma is aiming for market approval for the improved version of dasatinib in US, Europe, and all other major markets.