Fujifilm plans $20M U.S. facility for stem cell treatments

A host of companies are developing regenerative treatments that lean on stem cells. Seeing an opportunity, Japan’s Fujifilm will build a U.S. stem cell manufacturing facility not only for its own efforts but also as a CDMO.

The company said today that its Fujifilm Cellular Dynamics Inc. (FDCI) subsidiary will invest about $21 million to build a facility in Madison, Wisconsin, to “industrialize” induced pluripotent stem cell technologies for its pipeline of regenerative drugs and to manufacture iPS cells for others. It expects the facility to be ready by March 2020.

“To meet the growing demand for FCDI’s iPS cell platform, the state-of-the-art production facility will have a flexible cell culturing design to serve production requirements of both industrial quantities of cells, and small, diverse batches,” Seimi Satake, FCDI CEO, said in a statement. “By combining Fujifilm’s experience gleaned from the intricate process of manufacturing photographic film along with FCDI’s knowledge of cell reprogramming, genetic engineering and cell differentiation, the facility is poised to address the complex manufacturing processes of cell therapies.”

Fujifilm pointed to its investment in and work with Australian biotech Cynata Therapeutics as an indication of its experience. The Melbourne-based company is using a technology called Cymerus to manufacture mesenchymal stem cells to treat cytokine release syndrome, a severe immune reaction in some patients taking CAR-T treatments. Additionally, it said FCDI is already manufacturing iPS cell products for research by public institutions, pharma companies and academia.

A couple of other stem cell manufacturing facilities were announced toward the end of last year. Novo Nordisk, which is investigating stem cell treatments that might eventually cure Type 1 diabetes, is building out a facility in Fremont, California, that it has leased from stem cell biotech Asterias Biotherapeutics. Orchard Therapeutics is investing up to $90 million to build a manufacturing facility for its gene therapies program, also in Fremont.

https://www.fiercepharma.com/pharma-asia/fujifilm-plans-20m-u-s-facility-for-burgeoning-interest-stem-cell-treatments

Could Gilead, Amgen and AbbVie follow Bristol-Myers into megadeal territory?

Bristol-Myers Squibb’s Thursday announcement that it would nab Celgene for $74 billion brought “megamergers back to pharma,” as Credit Suisse analyst Vamil Divan put it in a note to clients. And the return has industry watchers wondering which company will be the next to follow suit.

Plenty of drugmakers could stand to pump up growth, and thanks to U.S. tax reform, they have the funds to do it. Just look at AbbVie, one of tax reform’s biggest winners, which also happens to be moving closer every day to a post-Humira future.

AbbVie certainly isn’t the only one out there with big assets set to wane over the next few years. Amgen is also coming up against biosimilar competition for Neulasta, and Bernstein analyst Ronny Gal has suggested the California company could ease the pain with a buyout of rare-disease focused Alexion. And it’s holding onto $30 billion in cash that it could put toward the cause, Bloomberg notes.

As analysts told the news service, a couple other big players belong on the M&A watch list, starting with Gilead. The Big Biotech has already attempted to mitigate its hepatitis C sales slide with one mammoth deal—its $12 billion pick-up of Kite—but with Kite’s CAR-T sales off to a slow start, it could use another, analysts contend. And they say companies like Clovis Oncology, which is struggling to keep its PARP inhibitor Rubraca competitive against rivals with more marketing muscle, could make a good target.

And then there’s Merck & Co., whose investors seem to be clamoring for some dealmaking action despite the company’s smashing success with PD-1 cancer fighter Keytruda.

Lucky for them, the New Jersey pharma giant’s executives are on board. “Let me start by saying that we’re pleased with the way in which our business is growing now, particularly in the oncology field, but that doesn’t make us comfortable,” CEO Ken Frazier told shareholders on Merck’s third-quarter call in October, adding that, “we have to continue to build our portfolio and build on our pipeline, and that’s why [business development] is an important priority for us going forward.”

Who’s not likely to take a seat the buyer’s table in 2019? Historical megamerger champion Pfizer, according to new CEO Albert Bourla.

“We continue not to see the need for any large-scale M&A activity at this time,” he said on Pfizer’s own third-quarter call.

https://www.fiercepharma.com/pharma/could-gilead-amgen-abbvie-follow-bms-into-megadeal-territory

JMP reiterates Outperform on Esperion after European agreement

JMP Securities analyst Jason Butler reiterated an Outperform rating and $153 price target on Esperion Therapeutics after the company announced a European commercialization agreement with Daiichi Sankyo for bempedoic acid and the BA/ezetimibe fixed dose combination. The analyst views this deal as “strong,” and sees Daiichi Sankyo as a compelling strategic fit “given its established commercial infrastructure and success in cardiovascular diseases in the region.”
https://thefly.com/landingPageNews.php?id=2844005

Achaogen in License Confirmation, Redemption Pact with Gates Foundation

On December 27, 2018, Achaogen, Inc. (the “Company”) entered into a License Confirmation Agreement and a Redemption Agreement with the Bill & Melinda Gates Foundation (the “Gates Foundation”) (together, the “2018 Agreements”) in connection with the amendment of certain provisions of the Grant Agreement (the “Grant Agreement”) and the Letter Agreement (the “Letter Agreement”) each previously entered into between the Company and the Gates Foundation and dated as ofMay 4, 2017.The 2018 Agreements were entered into following the de-prioritization of antibody work by the Company, which was the focus of the Company’s collaboration with the Gates Foundation.Among other things, the 2018 Agreements (a) terminated the Company’s obligations to conduct mutually agreed upon work, including work related the Company’s platform technology to develop and launch a product intended to prevent neonatal sepsis, (b) terminated the obligations of the Company to discover drug candidates intended to prevent neonatal sepsis and the obligation of the Gates Foundation to fund approximately $7.1 million in grants not yet received by the Company and (c) granted the Gates Foundation a non-exclusive license to intellectual property developed by the Company to the Grant Agreement and Letter Agreement in specified developing countries.

The Redemption Agreement also provided for the redemption by the Company of the 407,331 shares of the Company’s common stock (the “Gates Shares”) purchased by the Gates Foundation to a Common Stock Purchase Agreement between the Company and the Gates Foundation dated as of May 4, 2017 (the “Purchase Agreement”) for an aggregate redemption price of $5,737,082. The Company paid for the redemption of the Gates Shares with the unused portion of the restricted cash received by the Company to the original purchase of the Gates Shares under the Purchase Agreement.No unrestricted cash of the Company was used to fund the redemption.

https://marketexclusive.com/achaogen-inc-nasdaqakao-files-an-8-k-entry-into-a-material-definitive-agreement-2/2019/01/

Juno founders set on creating ‘epic’ new biotech with high-rolling investors

Steve Harr has been busy.

Over the past 9 months or so, the former Juno CFO who helped break ground on CAR-T tech has been creating a new biotech called Sana Biotechnology with some big goals in mind.

Sana is jumping from stage right into what it hopes will be the center ring of next-gen technology aimed at creating a new wave of cell and gene therapies that can be used off-the-shelf to go where needed to fix a variety of diseases — unbound by disease fields or even hub boundaries.

“We want to build something that is epic in its impact on patients,” says the CEO. Epic and enduring.

Harr isn’t talking money right now — “you can make your own conjectures” — but his 3 current backers tell me that money isn’t an issue.

https://endpts.com/juno-founders-set-their-sights-on-creating-an-epic-new-biotech-with-high-rolling-investors-at-their-back/

Constellation Updates on Trial of CPI-0610 in Myelofibrosis

Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, today provided an update on progress in the MANIFEST Phase 2 clinical trial of CPI-0610 in myelofibrosis (MF).

The Company also reviewed its 2018 accomplishments and announced its data disclosure plans for 2019.

As of December 10, 2018, each of the first four ruxolitinib-resistant second-line MF patients in MANIFEST remained on study. The two patients treated with a combination of CPI-0610 and ruxolitinib (i.e., CPI-0610 added onto existing treatment with ruxolitinib) have been treated for over 16 months. The two patients treated with CPI-0610 monotherapy have been treated for over 12 months. Each of the four patients has shown a reduction in spleen volume and improved hemoglobin levels. One of the combination therapy patients was transfusion dependent before therapy and converted to being transfusion independent after CPI-0610 was added to the patient’s regimen. As of our data cutoff, this patient’s response has persisted free of transfusions for over 52 weeks. Additionally, bone marrow biopsies before and after treatment were analyzed for the two patients on monotherapy, and both demonstrated a one-grade improvement in bone marrow fibrosis score as well as associated improvements in hemoglobin and platelets. Taken together, these results suggest that CPI-0610 may be modifying the underlying course of the disease in these ruxolitinib-resistant MF patients.

The Company has now opened 16 clinical trial sites in the U.S., Canada, and E.U. and enrolled 18 patients in MANIFEST. Only one patient has discontinued treatment, which was due to a non-drug-related serious adverse event. The recommended Phase 2 dose of CPI-0610 in the MANIFEST study is 125 mg once daily (may be titrated up), which is below the maximum tolerated dose of 225 mg once daily. Furthermore, in a Phase 1 clinical trial of CPI-0610, the Company also showed that the dose-limiting toxicity of thrombocytopenia was reversible and non-cumulative. Taken together, preliminary data suggest that CPI-0610 may have a wider therapeutic window and the potential for a differentiated toxicity profile relative to some other BET inhibitors, based on their published data.

Additional 2018 Accomplishments

‘During 2018, we generated encouraging preliminary clinical data for both CPI-0610 and CPI-1205, which led the Company to expand both clinical programs,’ said Jigar Raythatha. ‘We are particularly excited by the preliminary Phase 2 results we have seen thus far in CPI-0610 that demonstrate potential disease-modifying effects rather than primarily addressing the symptoms of the disease. In addition, we advanced CPI-0209, our second-generation EZH2 inhibitor that has the potential to broaden the patient populations treated with EZH2 inhibition, into IND-enabling development during the year.’

CPI-0610

Constellation announced that it enhanced and expanded the MANIFEST Phase 2 trial in October to stratify for transfusion dependence status. The Company also announced the planned initiation of a new arm to determine whether the combination of CPI-0610 and ruxolitinib in ruxolitinib-naive MF patients could improve on the benefit of ruxolitinib alone in first-line treatment of myelofibrosis.

Constellation announced that the FDA granted Fast Track status for CPI-0610 in myelofibrosis in November, a designation that facilitates the development and expedites the review of drugs to treat serious or life-threatening diseases and to fill unmet medical needs.

CPI-1205

Thirty-six patients have been enrolled in the Phase 1b portion of the ProSTAR clinical trial of CPI-1205 in metastatic castration-resistant prostate cancer (mCRPC) in combination with either abiraterone or enzalutamide. Constellation established the safety, pharmacokinetics, and pharmacodynamics of CPI-1205 in both the enzalutamide and the abiraterone arms. The Company also observed evidence of clinical activity in both arms.

Constellation announced the initiation of the Phase 2 portion of ProSTAR in December. Based on the clinical activity and safety profile demonstrated by CPI-1205 with either abiraterone or enzalutamide in the Phase 1b portion, Constellation expanded the Phase 2 portion of ProSTAR to study both combinations, i.e., a randomized trial of CPI-1205 + enzalutamide versus enzalutamide alone, as well as a single arm of CPI-1205 + abiraterone. While a low response rate and a short duration of response have been observed in clinical trials of second-line treatment of mCRPC generally, the unmet need in this setting is particularly great with abiraterone alone. Dosing has begun in the enzalutamide arm and will soon begin in the abiraterone arm.

CPI-0209

The Company nominated CPI-0209 as a development candidate in April. Preclinical data demonstrated that CPI-0209 engaged EZH2 more comprehensively and durably and produced more rapid tumor regression with lower and less frequent dosing compared with first-generation EZH2 inhibitors.

Corporate Development

Constellation completed a crossover financing in April and an initial public offering in July, together raising $160 million. As a result of these successful financings, Constellation expects to be able to fund its operations into the second quarter of 2020.

Constellation strengthened its management team by appointing a General Counsel and a Chief Scientific Officer. In addition, the Company expanded the board with appointments of two executives with extensive industry experience in prostate cancer and myelofibrosis.

A Look Ahead at 2019

‘2018 was all about execution, and we reached each of the business and R&D milestones that we set out to achieve for ourselves and our shareholders,’ continued Mr. Raythatha. ‘We expect 2019 to be an important year focused on data, as we are set up to deliver results from our ongoing studies throughout 2019.’

https://www.marketscreener.com/CONSTELLATION-PHARMACEUTI-44979177/news/Constellation-Pharmaceuticals-Provides-Update-on-MANIFEST-Clinical-Trial-of-CPI-0610-in-Myelofibro-27823526/

Aimmune, KKR in $170M Loan Agreement to Fund Commercialization, Pipeline

Aimmune Therapeutics Inc. (Nasdaq: AIMT), a biopharmaceutical company developing treatments for potentially life-threatening food allergies, today announced that it has entered into a $170 million loan agreement with an affiliate of KKR, a leading global investment firm.

“The addition of the KKR loan financing to Aimmune’s capital resources is expected to fully fund the commercialization of AR101, an investigational biologic oral immunotherapy for the treatment of peanut allergy,” said Eric Bjerkholt, Chief Financial Officer of Aimmune Therapeutics. “In addition, this financing secures resources to support the continued advancement of our pipeline of additional food allergy treatments, including the Phase 2 trial of AR201 for egg allergy, which is anticipated to commence this year.”

In December 2018, Aimmune submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for AR101 for the treatment of peanut allergy in children and adolescents ages 4–17 years based on data from the landmark Phase 3 PALISADE trial, which met its primary and key secondary endpoints, and from additional ongoing and completed AR101 clinical trials. The FDA has granted Breakthrough Therapy Designation to AR101 for the desensitization of peanut-allergic patients 4–17 years of age.

The loan agreement provides Aimmune with an up to $170 million term loan in three tranches. Forty million dollars was funded at close, with $85 million to follow upon FDA approval of AR101 and satisfaction of other customary borrowing conditions, and $45 million at the company’s option in 2020 upon the satisfaction of certain borrowing conditions. The loan can be prepaid at Aimmune’s discretion, at any time, subject to prepayment fees. Further information with respect to the term loan is set forth in a Form 8-K filed by Aimmune with the Securities and Exchange Commission on January 4, 2019.

Aimmune reported September 30, 2018, cash, cash equivalents and short-term investments of $255 million. With the $98 million equity investment from Nestlé Health Science announced in November 2018 and the $170 million KKR loan, assuming full borrowings under all tranches, Aimmune’s capital resources as of September 30, 2018, would have exceeded $500 million.

For KKR, the investment is part of the firm’s Health Care Royalty and Income strategy, which is focused on providing non-dilutive capital to companies for which KKR can help reach scale and achieve strategic objectives.

“Aimmune is leading the way in meeting the critical, growing need to offer treatment to the millions of people affected by food allergies,” said Emily Janvey, M.D., Head of Health Care Royalty and Income strategy at KKR. “We’re proud to help support Aimmune’s important work, especially as the company prepares to launch what could be the world’s first approved medical treatment for peanut allergy.”

https://www.biospace.com/article/releases/aimmune-therapeutics-and-kkr-enter-into-170m-loan-agreement-to-fund-ar101-commercialization-and-pipeline-advancement/