On January 13, 2020 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition") reported an update on its Nu Q Clinical Assays which use a magnetic particle-based assay format (Press release, VolitionRX, JAN 13, 2020, View Source [SID1234553125]). Volition has completely re-engineered its Nu.Q assays leading to a step-change improvement in analytical performance. Volition expects this enhanced analytical performance to translate into improved clinical performance in the studies to be carried out and reported in the coming months.

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Relative to Volition’s ELISA plate Nu.Q assay format, the magnetic particle-based assay format demonstrates:

A 10-20-fold improvement in analytical sensitivity of the assays.
Typical within-day reproducibility of quantitative test results below 3% (previously <10%).
Decrease in test result turnaround time from 6 hours to approximately 1 hour and 20 minutes, allowing much higher throughput.
The ability to be developed and processed on fully-automated Random-Access platforms (allowing the use of a wide range of commercial automated platforms).
Commenting on the assay transfer program Dr. Gaetan Michel, Chief Executive Officer of Belgian Volition said, "I am incredibly proud of the effort the whole team has made in the assay development program over the last two years and in particular, I would like to thank Mhammed Bougoussa, our recently appointed Assay Validation Expert for his significant contribution to the project. We now plan to finalize blood plasma sample pre-analytics with these assays and are excited to utilize these automated magnetic chemiluminescent assays in our clinical studies and aim to start reporting data during this quarter, and throughout 2020."

Volition has continued to create assets by:

Developing recombinant nucleosomes as calibrants which provide for assay specificity and reliable quantitation. Volition developed synthetic nucleosomes with its partners but has now brought this expertise in-house with the recent acquisition of Octamer, Gmbh announced January 10.
Internalizing key processes such as chemiluminescent antibody labeling and coating of magnetic beads. This secures our supply chain and provides flexibility to speed up our assay development work.
Moving from a microtiter plate format to a magnetic particle-based assay format. This improves assay kinetics and hence assay sensitivity and reduces assay time and increases assay throughput.
Moving from a traditional colorimetric endpoint format to a chemiluminescent endpoint. This further reduces background, leading to further improvements in assay sensitivity as well as greatly extending the usable range of the assays. Moreover, the combination of a chemiluminescent endpoint with a magnetic particle-based assay format greatly improved the specificity of Nu.Q assays.
Moving all these improvements onto an FDA-approved automated immunoassay analyzer which is currently in clinical use across USA and Europe. This further decreases assay processing time and greatly increases the reproducibility and reliability of assay results so that the same correct result is produced for any patient sample regardless of where or when the test is done or who operates the instrument.
Moving from blood serum to blood plasma as the test sample which reduces assay interference.

On January 13, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T) therapies for cancer and SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that they have entered into a clinical trial collaboration agreement (Press release, SpringWorks Therapeutics, JAN 13, 2020, View Source [SID1234553148]). This agreement will evaluate ALLO-715, Allogene’s investigational anti-B-cell maturation antigen (BCMA) AlloCAR T therapy in combination with SpringWorks’ investigational gamma secretase inhibitor (GSI), nirogacestat, in patients with relapsed or refractory multiple myeloma.

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Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of BCMA-targeted therapies.1 In addition, emerging clinical data suggest that a GSI may increase antitumor efficacy of BCMA-targeted autologous CAR T therapy in patients with relapsed and refractory multiple myeloma.23

"Autologous CAR T therapy has shown the potential for engineered cell therapy to treat multiple myeloma and provide significant benefits to patients. We believe allogeneic CAR T therapy is the next frontier in genetically engineered cell therapy for the treatment of cancer," said David Chang, M.D., Ph.D., President, CEO and Co-Founder of Allogene Therapeutics. "The search to find long-lasting and potentially curative therapies for patients with multiple myeloma continues to evolve. We are pleased with the progress of our ALLO-715 Phase 1 UNIVERSAL trial and are excited to explore the combination of ALLO-715 with nirogacestat as a means to further unlock the potential of allogeneic CAR T therapy in this disease."

Under the terms of the agreement, Allogene will sponsor and conduct the Phase 1 study to evaluate the safety, tolerability and preliminary efficacy of the combination, and will assume all development costs associated with the study. Allogene and SpringWorks will form a joint development committee to oversee the clinical study, which is expected to commence in the second half of 2020 pending discussions with regulators.

"Gamma secretase inhibition has emerged as a clinically validated mechanism to potentiate BCMA therapies and we believe that nirogacestat has the potential to become a cornerstone of BCMA combination therapy for patients with multiple myeloma," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We are delighted to partner with Allogene, a pioneer in the allogenic cell therapy field, to further explore nirogacestat in combination with an ‘off-the-shelf’ CAR T therapy for these patients where the need for treatment options remains great."

SpringWorks is currently enrolling patients in a global Phase 3, double-blind, randomized, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat in adults with progressing desmoid tumors.

About ALLO-715
ALLO-715, an AlloCAR T therapy targeting B-cell maturation antigen (BCMA), is currently in Phase 1 development as a potential novel treatment for multiple myeloma. Multiple myeloma is characterized by abnormalities in plasma cells that reproduce uncontrollably in the bone marrow of people with the disease,4 multiple myeloma is incurable for most patients, and most patients relapse despite the treatments available.5 Preclinical study results for ALLO-715 were published in the journal Molecular Therapy validating the potential for an AlloCAR T to treat multiple myeloma and demonstrating the ability for ALLO-715 to sustain potent anti-tumor responses in pre-clinical models. Allogene initiated the UNIVERSAL study in the third quarter of 2019.

ALLO-715 utilizes TALEN gene-editing technology pioneered and owned by Cellectis. Allogene has an exclusive license to the Cellectis technology for allogeneic products directed at the BCMA target. Allogene holds global development and commercial rights for this investigational candidate.

About Nirogacestat
Nirogacestat is an investigational, oral, selective, small molecule gamma-secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is pursuing a combination therapy approach to evaluate nirogacestat as a BCMA potentiator across modalities by collaborating with industry leaders. To date, SpringWorks has entered into two clinical collaborations to evaluate nirogacestat in combination with GlaxoSmithKline’s BCMA antibody-drug conjugate belantamab mafodotin and with Allogene’s allogeneic BCMA CAR-T cell therapy ALLO-715.

Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors (June 2018) and from the European Commission for the treatment of soft tissue sarcoma (September 2019). The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis (November 2018 and August 2019).

On January 13, 2020 Personalised cancer treatment is one step closer to becoming a reality for more patients, thanks to a Cancer Council Beat Cancer Project grant awarded to University of South Australia researcher Dr Stephanie Reuter Lange to explore how computer-based modelling can optimise cancer treatment and remove the need for expensive clinical trials (Press release, University of South Australia, JAN 13, 2020, View Source [SID1234554068]).

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Dr Reuter Lange’s $300,000 project is one of two UniSA projects successful in today’s Cancer Council Beat Cancer Project funding announcement with Professor Peter Hoffmann also securing $100,000 to further critical work in identifying the extent of endometrial cancer and where it has spread.

While cancer treatments are most successful when personalised to an individual, Dr Reuter Lange says most cancer medicines are still administered with a "one size fits all" approach.

"Despite substantial improvements in the treatment of cancer, three out of 10 patients will still not survive longer than five years, due to either cancer progression or death from severe treatment-related side effects," Dr Reuter Lange says.

"There is no field of medicine in which individualisation of medicines is more important than in the area of oncology. There is large variability in how patients respond to many cancer medicines, which can result in either undertreatment that leads to cancer progression, or overtreatment that can have significant toxic side effects.

"The concept of dose individualisation means we can tailor the amount of a drug administered to an individual patient to maximise tumour response and minimise side effects. My focus will be to use computer-based modelling methods to identify dose individualisation strategies for best treatment practice."

While the merits of individualised drug dosages are clear, conducting the large-scale clinicial trials required to implement the treatment in practice is a complex and costly process which means cancer treatments currently on offer remain standardised rather than personalised.

Dr Reuter Lange’s work uses the science of mathematical and stasitical models to characterise drug behaviour, helping clinicians make an educated decision on the most appropriate treatment regimes.

"This work will provide an evidence-basis for dose individualisation of cancer therapies, offsetting the need for the conduct of costly, large-scale clinical trials," she says.

"Ultimately this work will lead to improved patient outcomes and provide a framework on which treatment guidelines can be based for the optimal use of new and existing cancer therapies."

UniSA Professor Hoffmann’s research project will focus on developing less intrusive diagnosis and treatment techniques for endometrial cancer, the most diagnosed gynaecological cancer in Australia.

According to Professor Hoffmann, radiological imaging is unreliable in determining the stage of endometrial cancer, meaning the majority of patients have to undergo surgical staging (and removal of lymph nodes) even though the minority will actually have cancer that has spread to the lymph nodes (metastatic disease).

He says the Cancer Council SA funding will go towards identifying molecular tissue markers that indicate the presence of metastatic disease so that future patients may not need to undergo unnecessary radical surgery (Lymphadenectomy) to get an accurate diagnosis.

Established in 2011 Cancer Council’s Beat Cancer Project is a collaboration between Cancer Council SA, the State Government, SAHMRI and the universities and providing research funding to improve the lives of all South Australians impacted by cancer. For more information on the project, go to cancersa.org.au/research/beat-cancer-project.

On January 13, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported preliminary unaudited 2019 revenue and cash and investments at year end 2019, and provided 2020 revenue guidance for Crysvita in Ultragenyx territories (Press release, Ultragenyx Pharmaceutical, JAN 13, 2020, View Source [SID1234553076]).

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"We passed the $100 million revenue threshold in 2019 based on the strong launches of Crysvita and Mepsevii. We aim to build on this success in 2020 with the potential approvals of UX007 in LC-FAOD and Crysvita in TIO," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "This growing commercial foundation will continue to enable significant pipeline advancement as we execute on our gene therapy clinical studies and initiate multiple new clinical programs."

2019 Preliminary Revenue, 2020 Crysvita Revenue Guidance, and 2019 Ending Cash Position

2019 Preliminary Revenue (unaudited)

Total revenue for the year ended December 31, 2019 is approximately $102 million to $104 million. Total Crysvita revenue to Ultragenyx is approximately $86 million to $88 million in 2019, which includes collaboration revenue in the North American profit share territory, royalty revenue in the European territory from Kyowa Kirin Co. Ltd., and product revenue for Crysvita in other regions.

2020 Crysvita Guidance

For 2020, Crysvita revenue in the Ultragenyx territories is estimated to be between $125 million and $140 million. Ultragenyx territories include the North American profit share territory and other regions where collaboration revenue and product sales are recognized by Ultragenyx. The 2020 Crysvita revenue guidance excludes the European territory royalty revenue, the rights to which were sold to Royalty Pharma. Beginning January 1, 2020, the company will no longer receive cash payments from the EU territory royalty until the respective threshold amount is met; however, the company will continue to record the royalty as "non-cash" revenue.

The company is not providing total 2020 revenue guidance at this time. The preliminary revenue results are based on management’s initial analysis of operations for the quarter and year ended December 31, 2019. The 2019 revenue and cash position included in this release are preliminary and prior to the completion of review and audit procedures by Ultragenyx’s external auditors, and are therefore subject to adjustment. The Company expects to issue full financial results for the fourth quarter and fiscal year 2019 in February 2020.

2019 Ending Cash Position (unaudited) and 2020 Expected Net Cash Burn Rate

Cash, cash equivalents, and available-for-sale investments were greater than $750 million as of December 31, 2019, including proceeds of $320 million received from the sale of the company’s royalty interest in Crysvita in the European territory. The company also expects a more than 20 percent reduction in net cash burn (net cash used in operations plus capital expenditures) in 2020 compared to 2019.

Recent Updates and Upcoming Milestones

Crysvita for X-linked Hypophosphatemia: Non-dilutive $320 million royalty sale of future European royalties

In December, Ultragenyx sold to Royalty Pharma for $320 million its royalty interest in Crysvita in the European territory, where it is being commercialized by Kyowa Kirin Co., Ltd.
Crysvita for Tumor-Induced Osteomalacia (TIO): Supplemental Biologics License Application (sBLA) submitted

Ultragenyx submitted the sBLA to the U.S. FDA on December 18, 2019 and expects to hear back from FDA on submission acceptance and review designation in February 2020.
UX007 for Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD): NDA under review by U.S. FDA

The U.S. FDA accepted for review the New Drug Application (NDA) and has set a Prescription Drug User Fee Act (PDUFA) date of July 31, 2020. The FDA has indicated that it is not currently planning to hold an advisory committee meeting to discuss the application.
DTX301 for Ornithine Transcarbamylase (OTC) Deficiency: Positive data from higher cohort of Phase 1/2 study; data from prophylactic steroid cohort in second half 2020

Recent positive data from Cohort 3 indicated two confirmed responders and a potential third responder out of three total patients, as well as a new responder in Cohort 2. There are currently up to six responders of the nine dosed to date with a more consistent response at higher doses.

Ultragenyx is initiating a fourth cohort (n=3) using prophylactic steroids at the same dose as Cohort 3. The first patient is expected to be enrolled in the first half of 2020, and data from the prophylactic steroid cohort are expected in the second half of 2020.
DTX401 for Glycogen Storage Disease Type Ia (GSDIa): Positive data from Phase 1/2 study; enrollment complete in confirmatory cohort and data expected in first half 2020

Enrollment is complete in the confirmatory cohort of three patients at the second dose cohort, with data expected in the first half of 2020. Following the results of the confirmatory cohort, a Phase 3 study could begin in the second half of 2020.
GTX-102 for Angelman Syndrome: Partnered program with GeneTx; IND expected in first half 2020

An investigational new drug (IND) application is expected in the first half of 2020. In August 2019, Ultragenyx and GeneTx announced a partnership to develop GTX-102 with Ultragenyx receiving an exclusive option to acquire GeneTx.
UX701 for Wilson Disease: IND expected in second half 2020

An IND application is expected in the second half of 2020 for a new gene therapy for Wilson disease, a larger rare metabolic disease. UX701 will be the company’s second clinical program to utilize its HeLa manufacturing system. The Hemophilia A program partnered with Bayer uses the HeLa system and has released its first clinical data.
Ultragenyx to Present at 38ᵗʰ Annual J.P. Morgan Healthcare Conference

Dr. Kakkis will present on Tuesday, January 14, 2020 at 12:00 p.m. PT in San Francisco. The live and archived webcast of the presentation will be accessible from the company’s website at View Source

On January 13, 2020 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY), along with its subsidiaries together referred to as "Dr. Reddy’s", reported that the Company will be presenting at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco, California, USA (Press release, Dr Reddy’s, JAN 13, 2020, View Source [SID1234553093]).

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Erez Israeli, company’s Chief Executive Officer will present on Tuesday, January 14th, 2020 at 1:30 PM PST [3:00 AM IST on January 15th, 2020].