Mammoth Biosciences Raises $45 Million to Build Next Generation CRISPR Products For Therapeutics and Diagnostics

On January 30, 2020 Mammoth Biosciences, the company behind the world’s first CRISPR-based disease detection platform, reported an oversubscribed round of $45 million in its Series B (Press release, Mammoth Biosciences, JAN 30, 2020, webwire.com/ViewPressRel.asp?aId=254210 [SID1234553708]). The raise is led by Decheng Capital and has participation from Mayfield, NFX, Verily, Brook Byers, Plum Alley, Pacific 8, aMoon, and others. The capital will fuel the company’s further development of CRISPR diagnostics and next-generation CRISPR products as it extends its platform to include gene-editing and therapeutics as well. Mammoth is also exploring deep partnerships with biotech and pharmaceutical companies to leverage the Mammoth CRISPR platform to transform healthcare and deliver benefits to patients.

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CRISPR holds enormous promise for treating disease, with clinical trials for Cas9 already underway — a crucial step in bringing CRISPR out of the lab and into everyday life. But while this enzyme has shown first signs of success in the ex-vivo setting, challenges remain for in vivo applications, limiting the broad use of Cas9 for a wide field of diseases. Further, Cas9 cannot be used for CRISPR-based diagnostics, an emerging and ground-breaking application for Cas systems.

Mammoth is uniquely positioned to overcome these obstacles with its extensive portfolio of novel Cas systems that serve as a toolbox for applications in diagnostics, gene-editing, and therapeutics. The $45 million Series B will fuel the development of the CRISPR platform with a particular focus on the Mammoth-discovered and characterized Cas14. Cas14 is a unique enzyme that opens up new possibilities due to its extremely small size, diverse targeting ability and high-fidelity. These properties will enable Mammoth to achieve next-generation editing with a broader target range for both ex-vivo and in-vivo applications and is a foundation for enabling advanced CRISPR modalities such as targeted gene regulation, precision editing, and beyond.

Recently, industry veterans including Peter Nell, previously a co-founder of Casebia (a joint venture between Bayer and CRISPR Therapeutics) and Ted Tisch, previously an executive at Synthego and Bio-Rad, have joined the company to accelerate its growth as Chief Business Officer and Chief Operating Officer, respectively. Grail co-founder and previous Illumina board member Jeff Huber has joined the company’s board as an independent director and the Dean of the Stanford University School of Medicine, Lloyd Minor, has joined the Mammoth advisory board.

"As a team on the frontlines of discovery in CRISPR, we’ve seen firsthand the need for new tools to deliver on the therapeutic and diagnostic promise that this technology has to offer," explained Trevor Martin, CEO and Co-founder of Mammoth Biosciences. "In powering new products in addition to diagnostics, we’re enabling the full potential of our platform to read and write the code of life and to fully transform how we interact with biology."

Beyond Mammoth’s own initiative to develop the next generation of CRISPR products for gene-editing and therapeutics, the company has already seen significant traction in enabling access to its robust and expansive CRISPR IP. As a testament to its proprietary data and powerful CRISPR platform, Mammoth has partnered with Horizon Discovery, a global leader in bioproduction to develop best in class CRISPR tools for CHO cell line editing.

"One of our missions is to identify and develop the next wave of innovative healthcare companies and support them through investment and inclusion in our Partner’s Space program on Verily’s campus. Mammoth is clearly one of these companies, driving the next-generation of CRISPR products that researchers at the forefront of gene-editing and diagnostics truly need," remarked Andrew Harrison, head of business and corporate development at Verily. "With an experienced leadership team and the guidance of CRISPR pioneer Jennifer Doudna, Mammoth is well-positioned to close the gap between the discovery of new CRISPR systems and their application in diagnostics and therapeutics."

Mammoth is currently evaluating partnerships with companies adding complementary skills to leverage these new proteins in gene editing, therapeutic, and diagnostic applications to deliver on the promise of this groundbreaking CRISPR technology. For more information visit View Source

Black Diamond’s Upsized IPO Raises $201M to Advance Its Cancer Drug R&D

On January 30, 2020 Black Diamond Therapeutics reported unveiled technology that analyzes genetic data to discover new cancer drugs (Press release, Xconomy, JAN 30, 2020, View Source [SID1234553707]). The company has $201 million from an IPO to advance the development of drugs stemming from that technology.

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Black Diamond priced its IPO late Wednesday, selling 10.5 million shares for $19 apiece. That tops the company’s earlier target of 8.9 million shares in the range of $16 to $18 each. Those shares are expected to begin trading Thursday on the Nasdaq exchange under the stock symbol "BDTX."

Black Diamond’s technology, called Mutation Allostery Pharmacology (MAP), analyzes population-level genetic sequencing data in order to find mutations that drive cancer growth. These mutations are grouped into families, the company says in its IPO filing. Black Diamond aims to treat cancer, regardless of the type of tumor, by targeting specific families of mutations with small molecule drugs.

Lead Black Diamond drug BDTX-189 was designed to target the ErbB family of enzymes, specifically mutations in two proteins from this family: EGFR and HER2. These mutations are prevalent in breast, bladder, endometrial, gastric and colon cancers, as well as non-small cell lung cancer. In animal tests, Black Diamond reported that the drug stopped tumors from growing and also shrank them. The company expects to start a Phase 1/2 study testing BDTX-189 in the first half of this year.

Black Diamond’s pipeline also includes a preclinical drug in development for glioblastoma, an aggressive cancer affecting the brain or spinal cord. The company says in the filing that it is completing preclinical work on glioblastoma candidate leads and expects to select a candidate later this year.

The new IPO cash will be deployed across Black Diamond’s programs. According to the filing, $50 million is earmarked for completing the Phase 1 portion of the BDTX-189 Phase 1/2 study. Another $20 million is set aside for the glioblastoma program. Black Diamond plans to spend $25 million more to continue its drug discovery work.

Black Diamond was founded in 2014 by David Epstein and Elizabeth Buck. Three years later, they began working with venture capital firm Versant Ventures to develop the technology underpinning the company, according to the filing. Black Diamond was incubated in a drug discovery unit established by Versant before unveiling its technology in late 2018. Last January, the company closed an $85 million Series B round of financing. Prior to the IPO, Versant was Black Diamond’s largest shareholder, owning a 42 percent stake in the company, the IPO filing shows.

West to Host Fourth-Quarter and Full-Year 2019 Conference Call

On January 30, 2020 West Pharmaceutical Services, Inc. (NYSE: WST), a global leader in innovative solutions for injectable drug administration, reported that it will release fourth-quarter and full-year 2019 financial results before the market opens on Thursday, February 13, 2020, and will follow with a conference call to discuss the results and business expectations at 9:00 a.m. Eastern Time (Press release, West Pharmaceutical Services, JAN 30, 2020, View Source [SID1234553706]). To participate on the call, please dial 877-930-8295 (U.S.) or 253-336-8738 (International). The conference ID is 5587337.

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A live broadcast of the conference call will be available at the Company’s website, www.westpharma.com, in the "Investors" section. Management will refer to a slide presentation during the call, which will be made available on the day of the call. To view the presentation, select "Presentations" in the "Investors" section of the Company’s website.

An online archive of the broadcast will be available at the site three hours after the live call and will be available through Thursday, February 20, 2020, by dialing 855-859-2056 (U.S.) or 404-537-3406 (International). The conference ID is 5587337.

Vertex Reports Full-Year and Fourth-Quarter 2019 Financial Results

On January 30, 2020 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the full year and fourth quarter ended December 31, 2019 and provided full-year 2020 financial guidance (Press release, Vertex Pharmaceuticals, JAN 30, 2020, View Source [SID1234553705]).
"In 2019, our differentiated strategy of investing in serial scientific innovation to create transformative medicines delivered remarkable performance. This was marked by the early approval of TRIKAFTA, the rapid progression of our pipeline in additional diseases and continued financial growth as we continued to treat more patients with our medicines worldwide," said Jeffrey Leiden, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. "This success is the culmination of many years of hard work to build a team, a pipeline and a company that we believe will discover, develop and commercialize transformative medicines for years to come."
Fourth-Quarter and Full-Year 2019 Financial Highlights

^Non-GAAP product revenues exclude $155.8 million related to ORKAMBI in the fourth quarter and full year ended December 31, 2019. Please refer to Note 4 for further information.
^^ GAAP Net income and GAAP Net income per share – diluted included a benefit from income taxes of approximately $1.5 billion in the fourth quarter and full year ended December 31, 2018 due to the release of Vertex’s valuation allowance on the majority of its net operating losses and other deferred tax assets.

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Total GAAP and Non-GAAP product revenues increased 37% and 32%, respectively, compared to 2018, primarily driven by the global uptake of SYMDEKO and SYMKEVI in patients ages 12 and older, label expansions for the company’s CF medicines globally, and the early approval and launch of TRIKAFTA in the U.S.
GAAP net income decreased compared to 2018, largely driven by the release of Vertex’s tax valuation allowance in 2018.
Non-GAAP net income increased compared to 2018, driven by the strong growth in total product revenues.
Cash, cash equivalents and marketable securities as of December 31, 2019 were $3.8 billion, an increase of approximately $600 million compared to $3.2 billion as of December 31, 2018.

Combined GAAP and Non-GAAP R&D and SG&A expenses increased compared to 2018, primarily due to the incremental investment to support the global use of Vertex’s medicines and the expansion of Vertex’s pipeline in CF and other new disease areas. Combined GAAP R&D and SG&A expenses also increased compared to 2018 due to Vertex’s business development activities.

GAAP and Non-GAAP income taxes increased significantly compared to 2018 due to Vertex’s release of its valuation allowance on the majority of its deferred tax assets in the fourth quarter of 2018. GAAP and non-GAAP income taxes in 2019 include a provision for income taxes on Vertex’s pre-tax income using an estimated effective tax rate approximating statutory rates. This provision for income taxes includes a significant non-cash charge due to Vertex’s ability to offset its pre-tax income against previously benefited net operating losses. Refer to "Supplemental Income Tax Information" for discussion of the cash versus non-cash components of Vertex’s provision for income taxes.

Total GAAP and Non-GAAP product revenues increased 63% and 45%, respectively, compared to the fourth quarter of 2018, primarily driven by the early approval and launch of TRIKAFTA in the U.S. and the global uptake of SYMDEKO and SYMKEVI in patients ages 12 and older.
GAAP net income decreased compared to the fourth quarter of 2018, largely driven by the release of Vertex’s tax valuation allowance in the fourth quarter of 2018.
Non-GAAP net income increased compared to the fourth quarter of 2018, driven by the strong growth in total product revenues.

Combined GAAP and Non-GAAP R&D and SG&A expenses increased compared to the fourth quarter of 2018, primarily due to the incremental investment to support the global use of Vertex’s medicines and the expansion of Vertex’s pipeline in CF and other new disease areas.
GAAP and Non-GAAP income taxes increased significantly compared to the fourth quarter of 2018 due to Vertex’s release of its tax valuation allowance in the fourth quarter of 2018. Refer to "Full-Year 2019 Expenses" for further information. Refer to "Supplemental Income Tax Information" for discussion of the cash versus non-cash components of Vertex’s provision for income taxes.

Full-Year 2020 Financial Guidance
Vertex today provided its full-year 2020 financial guidance. A summary of the company’s current financial expectations is below:

"Entering 2020, Vertex has never been stronger," said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer. "We are well-positioned for both near- and long-term growth based on treating more people with our CF medicines and from other future medicines in diseases aligned with our strategy, including alpha-1 antitrypsin deficiency, APOL1-mediated kidney diseases, pain and severe hemoglobinopathies. Going forward, our financial strength will enable us to continue to significantly invest

in internal R&D and external innovation, which will provide access to new technologies, programs and expertise that will lead to further growth in the years ahead."

Clinical Development
Cystic Fibrosis (CF):

On October 21, 2019, the company announced that the U.S. Food and Drug Administration (FDA) approved TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for the treatment of CF in people ages 12 years and older who have at least one F508del mutation. TRIKAFTA is Vertex’s fourth breakthrough medicine approved to treat the underlying cause of CF.

On October 31, 2019, the company announced that the European Medicines Agency (EMA) has validated the marketing authorization application (MAA) for the elexacaftor, tezacaftor and ivacaftor triple combination regimen.

Enrollment is ongoing in a Phase 3 study evaluating the elexacaftor, tezacaftor and ivacaftor triple combination regimen in children with CF ages 6 to 11 years who have two F508del mutations and in children who have one F508del mutation and one minimal function mutation. Pending the results of the Phase 3 study, the company plans to submit a supplemental New Drug Application (sNDA) to the FDA in 2020 followed by additional submissions to other global regulatory agencies.
Alpha-1 Antitrypsin (AAT) Program:

VX-814: Enrollment is ongoing in the Phase 2 proof-of-concept study evaluating VX-814, the company’s first oral small molecule corrector for the treatment of alpha-1 antitrypsin (AAT) deficiency. Vertex expects to obtain data from this study in 2020.

VX-864: A Phase 1 study is ongoing in healthy volunteers evaluating VX-864, the company’s second investigational small molecule corrector for the treatment of AAT deficiency.
Sickle Cell Disease and Beta Thalassemia:

In November 2019, Vertex and its partner CRISPR Therapeutics announced positive, interim data from the first two patients with severe hemoglobinopathies – one patient with transfusion-dependent beta thalassemia and one patient with severe sickle cell disease – treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001 in the ongoing Phase 1/2 clinical trials. Enrollment is ongoing in both trials and the companies expect to provide additional data for this program in 2020.

APOL1-Mediated Kidney Diseases:

Vertex continues to advance a portfolio of molecules for the treatment of APOL1-mediated focal segmental glomerulosclerosis (FSGS) and other serious kidney diseases. In the fourth quarter of 2019, Vertex completed a Phase 1 study of its first investigational oral small molecule VX-147 in healthy volunteers. Vertex plans to initiate a Phase 2 proof-of-concept study in 2020 to evaluate the reduction in protein levels with VX-147.
Pain:

The company announced today that it has discontinued Phase 1 development of VX-961. The company continues to advance a portfolio of NaV1.8 inhibitors into the clinic. As part of this strategy, Vertex plans to advance an additional molecule into clinical development in the first half of 2020.
Type 1 Diabetes:

Vertex plans to advance its cell therapy program for the treatment of type 1 diabetes into clinical development in late 2020 or early 2021.

Notes and Explanations
1: The company records gains and losses related to changes in the fair value of its strategic investments to "Other income, net."
2: In the fourth quarter of 2018, the company recorded a non-cash benefit from income taxes of approximately $1.5 billion related to the release of its valuation allowance on the majority of its net operating losses and other deferred tax assets. As a result, the company recorded deferred tax assets of $1.5 billion on its consolidated balance sheet as of December 31, 2018, which were previously subject to its valuation allowance. Starting in the first quarter of 2019, the company began recording a provision for income taxes on its pre-tax income using an estimated effective tax rate that approximates statutory rates. The provision includes a significant non-cash charge due to the company’s ability to offset its pre-tax income against previously benefited net operating losses. The company expects the majority of its tax provision to represent a non-cash expense until its net operating losses have been fully utilized. As of December 31, 2019, the company’s federal net operating losses and credits that were available to offset future pre-tax income were approximately $3.5 billion.
3: During the three and twelve months ended December 31, 2019, the increase in the fair value of the contingent consideration relates to payments potentially payable to Exonics’ former equity holders. During the three and twelve months ended December 31, 2018, the company consolidated the financial statements of a variable interest entity, or VIE, resulting in changes in the fair value of contingent consideration.
4: "ORKAMBI adjustment" in the three and twelve months ended December 31, 2019 includes an adjustment to net product revenues and cost of sales related to the conclusion of the early access program for ORKAMBI in France in the fourth quarter of 2019. The company had previously recognized a portion of net product revenues related to ORKAMBI distributed through the early access program in France. As a result, the company recognized an adjustment to increase net product revenues and cost of sales, which related to prior period shipments of ORKAMBI distributed through the early access program in France. The company has excluded the adjustment to net product revenues and cost of sales from its Non-GAAP measures for the three and twelve months ended December 31, 2019. Beginning in 2020, the company does not expect to adjust any revenues from its GAAP net product revenues.

5: "Collaborative revenues and expenses" in the three and twelve months ended December 31, 2019 and 2018 primarily related to collaborative upfront and milestone payments. "Collaborative revenues and expenses" in the three and twelve months ended December 31, 2018 also included revenues and expenses attributable to our VIE’s operations.
6: "Acquisition-related costs" in the three and twelve months ended December 31, 2019 primarily related to costs associated with the company’s acquisitions of Semma and Exonics. There were no comparable amounts during the three and twelve months ended December 31, 2018.
7: In the three and twelve months ended December 31, 2019, "Estimated income taxes related to non-GAAP adjustments to pre-tax income" primarily related to (i) stock-based compensation (including an adjustment for excess tax benefits related to stock-based compensation), (ii) increases or decreases in the fair value of the company’s strategic investments and (iii) collaborative upfront payments. In the three and twelve months ended December 31, 2018, "Estimated income taxes related to non-GAAP adjustments to pre-tax income" were related to a provision for income taxes attributable to the company’s VIE and excess tax benefits related to stock-based compensation.

01/30/2020: THERADIAG announces annual revenue of € 9.6 million in 2019, up 8.3%

On January 30, 2020 THERADIAG (ISIN: FR0004197747, Mnemonic: ALTER), a company specializing in in vitro diagnostics of autoimmune diseases and Theranostics reported its consolidated annual sales and its cash level at December 31, 2019, data under audit (Press release, Theradiag, JAN 30, 2020, View Source [SID1234553704]).

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2019 consolidated revenue of € 9.6 million

As of December 31, 2019, Theradiag generated revenue of 9.6 million euros compared to 8.9 million in 2018, an increase of + 8.3% in line with the strategic axes set by the company.

The Theranostics activity recorded strong growth of + 10.5%, driven by sales of routine LISA TRACKER kits which now represent the company’s recurring activity in this segment. These kit sales exceeded a threshold with 4.3 million euros on the 2019 annual global (vs. 3.9 million at December 31, 2018). In the future, the Theranostics activity may be assimilated to this recurring activity of kit sales, now well in place, and the company will communicate on this one element of global Theranostics.

In France, where the model is now established, sales in Theranostics were particularly satisfactory with growth of 19%.

In the United States, Theradiag has concluded a year of transition reflecting the exit of its former partner in this territory. The transfer to its new partner Halio DX is gradual and will be finalized at the end of the first quarter of 2020.

In export, the company maintains a very satisfactory level of sustained activity, particularly in Spain and the United Kingdom, two strategic countries.

The In Vitro Diagnostics (IVD) activity posted overall growth in sales of + 6.0% with 5.2 million euros at the end of December 2019. It should be noted that this growth includes 1 st semester non-recurring instrumentation sales . Aside from this exceptional element, sales in this historic business segment are, as expected, slightly down. Theradiag pursues in this historical segment, in addition to its primary activity of autoimmunity, a strategy of niche specialization, such as genetics or male fertility.

Cash position

At December 31, 2019, Theradiag’s free cash flow stood at 2.9 million euros compared to 3.4 million euros at December 31, 2018 and 3.2 million euros at June 30, 2019.

Bertrand de Castelnau, CEO of Theradiag commented, "Theradiag and all the teams have made good progress in 2019: new products, new partners, new markets. We followed our roadmap with the objective of developing growth in our strategic priority markets, without compromising the investments necessary for the future of Theradiag. Priority has been given to restructuring the mix of our activities and setting milestones for internationalization, in market segments with higher profitability potential. We are staying the course to gradually improve our financial performance indicators. "

"This year is indeed a pivotal year. The overall sales growth is positive and points in the right direction. The development of the strategy around partnerships centered on Theranostics is gradually unfolding, we have recorded great successes this year and keep our commitment to innovation which is one of our key success factors. " Added Pierre Morgon, Chairman of the Board of Directors of Theradiag.

Reminder of the main events of 2019

Partnership with three new strategic distributors in Asia, December 2019
CE marking of the new i-Track 10 automated system for monitoring biotherapies, November 2019
Strategic agreement with PredictImmune for the marketing of PredictSURE IBD in French-speaking European countries, October 2019
Signing of an agreement with Halio DX as part of its development in the United States, May 2019
Signature of a development and distribution agreement with Immunodiagnostic Systems (IDS) regarding access to the latest generation IDS-i10 controller , April 2019
End of legal dispute with HOB Biotech, April 2019

Financial calendar:

2019 annual results , March 18, 2020, after market close
Annual General Meeting , May 14, 2020

Next congresses in which Theradiag participates:

12-15 February 2020 15 th congress ECCO (European Crohn’s and Colitis Organization), Vienna, Austria
5-6 March 2020: Days of the Syndicate of Young Medical Biologists – Biomed-J 2020, Paris
March 6-7, 2020: Seminar Therapeutic Study of Inflammatory Conditions of the Digestive Tube (GETAID), Paris
March 26-29, 2020: Francophone Days of Hepato-gastroenterology and Digestive Oncology 2020 (JFHOD), Paris.