On August 2, 2021 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, reported its financial results for the second quarter 2021 and reaffirmed its financial guidance for 2021 (Press release, Ultragenyx Pharmaceutical, AUG 2, 2021, View Source [SID1234585538]).

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"In the first half of 2021 we have advanced all our commercial, clinical, and regulatory priorities. This has led to meaningful revenue growth in the second quarter and has positioned us well as we enter a period of significant execution on our clinical programs in the second half of this year," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "We have one of the most robust late-stage pipelines in both gene therapy and other biologics for rare diseases and are on track to initiate four pivotal clinical trials over the next six months."

Second Quarter 2021 Financials

In the second quarter 2021, Crysvita revenue in Ultragenyx territories1 increased 38% versus the second quarter 2020. This increase is driven by demand from pediatric and adult patients with X-linked hypophosphatemia (XLH) and patients with tumor induced osteomalacia (TIO), which became Crysvita’s second approved indication in the United States in June 2020.

Dojolvi revenue in the second quarter 2021 continued to build on the launch momentum after the U.S. Food and Drug Administration (FDA) approval in June 2020. As of the end of the second quarter 2021, the company has received approximately 270 completed start forms from approximately 130 unique prescribers. This has led to approximately 220 patients on reimbursed therapy as of the end of June 2021.

Second quarter 2021 revenue included $22.0 million related to the technology transfer as part of the Daiichi Sankyo strategic manufacturing partnership around the HeLa PCL and HEK293 technologies. This revenue is expected to taper significantly through the end of this year as these activities come to a close.

Total operating expenses of $169.8 million in the second quarter 2021 increased 36% or $45.0 million versus the second quarter 2020, primarily driven by pipeline advancements including four registrational studies. For the year, total operating expenses are expected to increase modestly as the company continues the commercial launch of Dojolvi and supports six clinical programs, including four pivotal studies.

Net cash used in operations for the six months ended June 30, 2021 was $224.7 million, compared to net cash used of $7.8 million for the same period in 2020 which included approximately $135 million of operating cash received in 2020 from Daiichi Sankyo related to the collaboration and license agreement. Cash, cash equivalents, and marketable debt securities were $973.8 million as of June 30, 2021.

2021 Financial Guidance

Crysvita Guidance in Ultragenyx Territories
The company reaffirms the 2021 guidance range for Crysvita that was provided at the beginning of the year. This range is $180 million to $190 million and includes the North American profit share region and the other regions where product sales are recognized.

Second Quarter 2021 Revenue and Selected Financial Data Tables

Program Updates and Upcoming Milestones

Crysvita for the treatment of X-Linked Hypophosphatemia, or XLH

The European Commission (EC) approved Crysvita for self-administration as a treatment option when recommended by the treating physician, for pediatric and adult patients with XLH.
GTX-102 for the treatment of Angelman Syndrome, partnered with GeneTx

Health Canada (HC) cleared a protocol amendment and the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) approved a Clinical Trial Application to initiate the Phase 1/2 study in Canada and the U.K, respectively.
Following a productive meeting with the FDA, GeneTx submitted an amended protocol. The companies have received feedback on the amended protocol and will make additional revisions in order to resume the study in the U.S.
The Phase 1/2 study is expected to begin in the U.K. and Canada in the second half of 2021, with early clinical data from some patients in the study expected before the end of the year.
DTX401 for the treatment of Glycogen Storage Disease Type Ia, or GSDIa

Longer-term Phase 1/2 data were presented at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2021 Annual Meeting demonstrating a durable response from all nine patients lasting up to more than 2.5 years following treatment with DTX401.
Operations are underway to initiate a Phase 3 study with a 48-week primary efficacy analysis period with the plan to enroll approximately 50 patients 8 years of age and older, randomized 1:1 to DTX401 (1.0 x 10^13 GC/kg dose) or placebo. The coprimary endpoints are the reduction in oral glucose replacement with cornstarch while maintaining or improving glucose control assessed by continuous glucose monitoring.
The first patient in the Phase 3 study is expected to be dosed in the second half of 2021.
DTX301 for the treatment of Ornithine Transcarbamylase, or OTC, Deficiency

Longer-term Phase 1/2 data were presented at the ASGCT (Free ASGCT Whitepaper) 2021 Annual Meeting showing a response from all three patients at the Phase 3 dose and a total of 6 of 9 responders in the first three cohorts of patients enrolled. This response included durable metabolic control lasting up to more than three years following treatment with DTX301 in patients with OTC deficiency.
Operations are underway to initiate a Phase 3 study that will include a 64-week primary efficacy analysis period and enroll approximately 50 patients 12 years of age and older, randomized 1:1 to DTX301 (1.7 x 10^13 GC/kg dose) or placebo. The co-primary endpoints are the percentage of patients who achieve a response as measured by discontinuation or reduction in baseline disease management and 24-hour plasma ammonia levels.
The first patient in the Phase 3 study is expected to be dosed in the second half of 2021.
UX701 for the treatment of Wilson Disease

Operations are underway to initiate a seamless, single-protocol Phase 1/2/3 study. The first part of the study will enroll approximately 27 patients (nine per cohort), randomized 2:1 to DTX701, manufactured using the company’s proprietary HeLa 2.0 producer cell line (PCL) process at the 2,000 liter scale, or placebo. The dose cohorts will be enrolled sequentially using ascending doses. The patients will be followed for 52 weeks before transitioning to long-term follow-up and selecting a pivotal dose. The dose will be determined based on the safety profile, changes in biomarkers of copper metabolism, and the reduction in the use of the current standard of care.
The first patient in the Phase 1/2/3 study is expected to be dosed in the second half of 2021.
UX053 for the treatment of Glycogen Storage Disease Type III, or GSDIII

UX053 was granted Orphan Drug Designation (ODD) by the FDA and European Medicines Agency (EMA), highlighting the significant unmet need for patients with GSDIII.
The first patient in the Phase 1/2 study is expected to be dosed in the second half of 2021.
1: Ultragenyx territories include the collaboration revenue from the North American profit share territory and other regions where revenue from product sales are recognized by Ultragenyx. This excludes the European territory revenue, which is recognized as non-cash royalty revenue since the rights were sold to Royalty Pharma in December 2019.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Monday, August 2, 2021, at 2 p.m. PT/ 5 p.m. ET to discuss the second quarter 2021 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 3654725. The replay of the call will be available for one year.

On August 2, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that the FDA has authorized Sorrento’s IND application for the Phase 1 clinical testing of its allogeneic anti-CD38 Dimeric Antigen Receptor (DAR) – T Cell therapy for relapsed or refractory multiple myeloma (Press release, Sorrento Therapeutics, AUG 2, 2021, View Source [SID1234585537]). The proprietary CD38 DAR-T cell therapy candidate demonstrated strong cytotoxic activity in preclinical studies. DAR-T product candidates are produced using Sorrento’s proprietary, non-viral knockout-knockin (KOKI) technology, which potentially allows for improved specificity, stability and potency, and enables an off-the-shelf treatment approach, thereby eliminating the need for patients to undergo leukapheresis and undesirable treatment delays to perform cell harvesting, manufacturing and release prior to treatment for each individual cancer patient.

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Sorrento’s KOKI-enabled DAR-T platform uses DAR-modified T cells from a normal healthy donor which are engineered to be specific to the cell surface marker of interest, in this case CD38, a clinically validated antigen in myeloma, to target tumor cells. The combination of KOKI and DAR-T technologies offers potential advantages over conventional CAR-T therapies, including removing the ability for DAR-expressing T cells to illicit undesired immune reaction to the cancer patient, thereby reducing or eliminating the possibility of graft versus host disease (GvHD) following treatment. Additionally, once DAR-T cells are manufactured, they can be stored at the clinic site, allowing patients to be screened and treated within days. This is compared to existing approved CAR-T therapies, which typically require 6-8 weeks of screening, cell production and qualification before a patient can receive treatment. Because of this timeframe, it is not unusual for cancer patients to no longer be eligible for CAR-T treatment due to disease progression. Also, autologous CAR-T cells pose several manufacturing challenges, including issues that relate to quality control and single-lot-release, and often do not meet the release criteria following the manufacturing process. DAR-T technology is designed to potentially provide a significant advancement to the timeliness and potency of treatments for patient populations who have already undergone multiple rounds of chemotherapy and are suffering from persistent disease.

DAR-T technology is readily adaptable to dozens of cancer targets and Sorrento has developed a preclinical product pipeline with specific fully human antibodies discovered from Sorrento’s G-MAB library. Sorrento expects to file additional IND applications now that the first DAR-T Phase 1 trial has been cleared to proceed by the FDA.

"This FDA clearance of our first allogeneic DAR-T cell therapy is a seminal event for our cutting-edge KOKI and DAR-T technologies," said Henry Ji, Ph.D., Chairman and CEO of Sorrento. "We foresee the first "Off-the-Shelf" DAR-T trial will open the door to numerous other DAR-T cell therapies for other indications to follow."

About the DAR-T Platform

Sorrento’s DAR-T technology is a proprietary, next-generation cell therapy platform that offers potential advantages over conventional Chimeric Antigen Receptor (CAR) T cell therapy:

The proprietary DAR construct utilizes a natural antibody Fab (antigen-binding fragment) structure instead of an artificial scFv (single-chain variable fragment) sequence.
Preclinical in vitro and in vivo studies have demonstrated that DAR-T cells provide better target specificity and functionality, due to higher inherent stability of the Fab and stronger affinity of DAR vs. CAR receptors on the T cell surface.
DAR-T cells may reduce potential undesirable side effects, such as CAR-T induced cytokine release syndrome (CRS) and graft-versus-host disease (GvHD).
About KOKI Technology

Sorrento’s proprietary, non-viral knockout-knockin (KOKI) technology provides DAR-T cells with several potential benefits over virus-based transduction currently used for CAR-T therapies:

"Off-the-Shelf": DAR-T cells are cryo-preserved engineered T cells designed to be delivered to patients on-demand without delays in treatment due to the lengthy and individualized manufacturing process for CAR-T.
"Allogeneic": DAR-T cells are produced from pre-screened healthy volunteers; while autologous CAR-T cells are patient-specific and made from and for individual cancer patients.
"Mass Production": DAR-T cell manufacturing is scalable (potentially hundreds to thousands of doses per manufacturing run) and can meet high demand while autologous CAR-T cell therapy requires a single-lot-release process that can only be performed one patient at a time.

On August 2, 2021 Oncternal Therapeutics (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that management will participate in the BTIG Virtual Biotechnology Conference being held August 9-10, 2021 (Press release, Oncternal Therapeutics, AUG 2, 2021, View Source [SID1234585536]).

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BTIG Virtual Biotechnology Conference – August 9-10, 2021

James Breitmeyer, President and Chief Executive Officer will present a corporate overview on Monday, August 9th at 12:00pm (ET), and the company will be available for one-on-one meetings.

On August 2, 2021 M2GEN, a company focused on transforming cancer care through data and informatics, reported the appointment of Jim Gabriele as President and Chief Executive Officer (Press release, M2Gen, AUG 2, 2021, View Source [SID1234585535]). Mr. Gabriele is a seasoned entrepreneur and data science leader who most recently served as Senior Vice President and Chief Strategy & Data Science Officer, Medical Devices Sector, at Johnson & Johnson.

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Mr. Gabriele was selected to lead M2GEN based on his track record of leading growth initiatives and digital transformations, deep understanding of biopharma, and capability-building skills in key technology and data-analytics that are critical priorities for M2GEN. M2GEN has established one of the largest and most comprehensive linked clinical and genomic databases in the country, empowering innovative, collaborative cancer research and supporting the development of novel oncology drugs by its biopharmaceutical partners. M2GEN runs one the world’s largest observational research studies in cancer, which tracks patients throughout their lifetime, links longitudinal clinical data with molecular information, and enables a deeper understanding of a patient’s disease.

"M2GEN is at an important inflection point in terms of its growth and commercial opportunity," said Sandi Peterson, Chairman of M2GEN, Clayton, Dubilier & Rice Partner, and former group worldwide chairman of Johnson & Johnson. "Jim brings tremendous expertise and experience to help establish M2GEN as the data partner of choice for healthcare providers and biopharmaceutical companies, leveraging technology to inform critical innovation in cancer treatment. We are very excited to welcome him to the team to lead the company’s next phase of innovation and expansion."

Mr. Gabriele has more than 30 years’ experience as a senior executive at leading pharmaceutical, medical device and consulting organizations. Most recently, as Senior Vice President and Chief Strategy & Data Science Officer for Medical Devices at Johnson & Johnson, he led global strategy development, pricing strategy, data science, data strategy, digital customer experience and business insights. Prior to that, he held senior strategy and data science roles in the Johnson & Johnson Pharmaceutical organization. Previously, Mr. Gabriele built and served as Managing Director and Operating Partner for Henry Rak Consulting Partners, a successful strategy and analytics company serving large global Pharmaceutical, Medical Device and CPG companies. It was acquired by McKinsey & Company and later renamed HRC. Mr. Gabriele received a BA in Economics & Government from the College of William & Mary and an MBA from Harvard Business School. He serves on the advisory board of Finpay Holdings.

"I believe M2GEN is poised to fundamentally change the way cancer is studied and treated," said Mr. Gabriele. "I am delighted to join the talented team at M2GEN to support its next phase of growth, drive operational excellence, and build a flexible and scalable platform that furthers our mission to connect patients to a cure by accelerating the discovery, development and delivery of more personalized therapies."

Mr. Gabriele succeeds Helge Bastian, PhD. "Helge strengthened the foundation for the continued growth of M2GEN, and we would like to thank him for all of his contributions to the business," said Ms. Peterson. Dr. Bastian is leaving to pursue other career endeavors.

On August 2, 2021 Keros Therapeutics, Inc. ("Keros") (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, reported the appointment of Simon Cooper, M.B.B.S, as Keros’ Chief Medical Officer, effective as of August 2, 2021 (Press release, Keros Therapeutics, AUG 2, 2021, View Source [SID1234585534]).

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"We are pleased to welcome Dr. Cooper to Keros as Chief Medical Officer," said Jasbir S. Seehra, Ph.D., Chief Executive Officer of Keros. "As we continue to advance our clinical pipeline, we will benefit tremendously from his clinical and development experience, as well as his deep understanding of the regulatory landscape."

Dr. Cooper joins Keros Therapeutics after most recently serving as the Senior Vice President, Chief Medical Officer of Kadmon Holdings, Inc. Prior to that, Dr. Cooper served as Chief Medical Officer of Anokion SA, a private biopharmaceutical company, from January 2019 to February 2021. From May 2016 to December 2018, Dr. Cooper served as Asset Strategy Leader at AbbVie Inc. From July 2014 to May 2016, Dr. Cooper served as Vice President, Global Project Head, Immunology and Inflammation, at Sanofi S.A. From November 2012 to July 2014, Dr. Cooper served as Global Program Medical Director at Novartis International AG. Prior to that, Dr. Cooper served as Executive Director, Clinical Research at Human Genome Sciences. Earlier in his career, Dr. Cooper worked in various clinical research positions at MedIumme Ltd., Roche, Napp Pharmaceutical Research Limited, Wyeth Research and Medeval Limited. Dr. Cooper received an M.B.B.S. from University of Newcastle upon Tyne in the United Kingdom before undertaking his higher medical training in Oxford, UK.

"Keros has made meaningful progress toward advancing its pipeline of novel therapeutics that target the Transforming Growth Factor-Beta superfamily for the treatment of patients in significant areas of unmet need," said Dr. Cooper. "I’m excited for the potential of KER-050, particularly given the Company’s preclinical data demonstrating its ability to potentially target early through terminal stages of erythropoiesis. I look forward to guiding KER-050, KER-047, KER-012 and future programs through and into the clinic and making an important contribution to Keros’ future success."

Dr. Cooper is succeeding Claudia Ordonez, M.D., who will be pursuing other opportunities. Dr. Ordonez will provide consulting services to Keros until September 15, 2021. "We extend our gratitude to Dr. Ordonez for the pivotal role she played in advancing KER-050 into a Phase 2 clinical trial and helping transform Keros Therapeutics into a publicly-traded biopharmaceutical company with a promising clinical pipeline," continued Dr. Seehra.