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/

AbbVie Forges $105 Million+ CD39 Inhibitor Alliance With Tizona

Privately-held Tizona Therapeutics snagged $105 million in upfront cash as its cancer antibody TTX-030 is the centerpiece of a collaborative effort with Illinois-based AbbVie.

The two companies intend to combine their R&D capabilities with a focus on CD39-targeted therapeutics. CD39 is the enzyme that is responsible for a key immune regulatory action. The ATP-adenosine axis has become a focus of research in the tumor microenvironment due to its ability to control the inflammatory and suppressive activities of immune cells. CD39 is the enzyme responsible for that action. Tizona’s TTX-030 is an inhibitor of CD39. An investigational new drug application for TTX-030 has been accepted by the U.S. Food and Drug Administration.

The idea is that by blocking the actions of CD39, TTX-030 will prevent the formation of immune suppressive extracellular adenosine. In addition to preventing the formation of suppressive adenosine, TTX-030 also prevents the degradation of ATP. By doing so, that preserves its ability to stimulate dendritic and myeloid-derived cells responsible for innate immunity and immune cell priming necessary for adaptive immunity, the company said.

It’s this potential impact on the tumor microenvironment that caught AbbVie’s attention. Mo Trikha, head of oncology early development at AbbVie, said there is tremendous promise in exploring ways that the tumor microenvironment can be modulated to inhibit the growth of cancer cells.

“The Tizona team has generated compelling preclinical data for their TTX-030 program, and we look forward to a productive collaboration focused on rapidly advancing this novel first-in-class antibody,” Trikha said in a statement.

Courtney Beers, head of immunology at South San Francisco-based Tizona, which launched in 2016, noted that tumors can employ multiple strategies to create a tolerogenic microenvironment. That microenvironment reduces the immune system’s ability to detect and fight cancer, she said.

“Preclinical research shows that inhibiting CD39 may hold the key to restoring and bolstering immune responses against tumors. In AbbVie, we have a partner who shares our passion for science and commitment to delivering breakthrough innovation to patients with cancer,” Beers said in a statement.

Under terms of the deal, AbbVie handed over $105 million in upfront funding for the exclusive option of licensing Tizona’s CD39 program, including TTX-030. Additionally, AbbVie said it has made an equity investment in Tizona, but terms of that investment were not disclosed in the announcement.

Tizona will lead clinical development through completion of Phase 1b studies, after which AbbVie has an exclusive option to lead global development and commercial activities. Tizona retains an option to co-develop and co-promote in the United States and is eligible for success-based development and commercial milestones and tiered royalties on net sales.

https://www.biospace.com/article/abbvie-forges-105-million-cd39-inhibitor-alliance-million-with-tizona/

BioNTech Teams up With Sanofi to Target Solid Tumors in $91.5 Million Deal

Days ahead of the J.P. Morgan Healthcare Conference, Germany-based BioNTech extended its three-year-old collaboration with Sanofi as the companies look to co-develop the first cancer immunotherapy candidate for solid tumors.

As part of the deal, the French pharma giant will invest about $91.5 million in equity in BioNTech, a privately-held company. The investment follows BioNTech’s 2018 decision to exercise one of the option rights under the 2015 agreement to co-develop and co-commercialize the immuno-oncology candidate. The two companies will work to develop an investigational therapy that includes an mRNA mixture encoding immunomodulatory cytokines that are injected directly into the tumor. Local administration of immunotherapies to the tumor microenvironment provides the opportunity to stimulate innate and adaptive immune responses against tumors, while potentially avoiding toxicities related to systemic administration of immuno-modulatory therapeutics.

BioNTech Chief Operating Officer Sean Marett told BioSpace that the Sanofi deal is good for both companies as it furthers the relationship between the two as they look for more efficacious treatments in cancer.

The program being jointly developed between the companies has moved from concept to the clinic in a span of only three years. The belief is that targeted mRNA therapies may have the potential to be effective for cancer patients. BioNTech’s research focus for oncology is one that requires distinct approaches. Marett said each tumor is different and it requires the development of individualized products for each patient. With cancerous tumors, Marett noted that there can be a number of mutations at the molecular levels. Those mutations make great targets because they’re new cells and “haven’t been through the check-in process of the immune system.”

If you can boost the immune system against them, you can fight them,” said of the mutations.

The partnership is one of many that BioNTech has been able to forge since its founding in 2008. In addition to Sanofi, the company also has partnerships with Genentech, Pfizer, Genmab, Eli Lilly, Genevant and Bayer Animal Health. In November 2018, the company forged an agreement worth up to $425 million with Pfizer to develop mRNA-based flu vaccines. Then, in November, the company inked a deal with the University of Pennsylvania to develop novel nucleoside-modified mRNA vaccine candidates for the prevention and treatment of various infectious diseases. Earlier this summer, the company forged its agreement with Genevant to develop five therapeutics to treat rare diseases with high unmet medical need using its mRNA drug discovery platform. The companies will combine Genevant’s lipid nanoparticle (LNP) delivery technology and BioNTech’s mRNA platform to develop the best-in-class therapeutics

Marett said BioNTech appreciates the idea of co-development deals, because both parties are at the table determining the course of an asset. As the company looks to bring immune-oncology products to market, particularly in places like the United States, he said it helps to have partners who have a footprint in the area, like Sanofi and Genentech.

BioNTech has developed four broad technology platforms, including an mRNA-based platform that is focused on oncology and infectious diseases, as well as a cell and gene therapy platform. The company also has a protein therapeutics platform and a small molecule development platform. Currently, BioNTech has five programs in the clinic, with more expected over the course of this year. Additionally, the company anticipates a rapid expansion of its pre-clinical pipeline.

In addition to its mRNA programs, BioNTech is also working on developing a CAR-T treatment for solid tumors. So far, the only CAR-T treatments that have been approved by the FDA are for blood cancers. However, Marett said the company believes they have one program that might be a game-changer when it comes to using CAR-Ts against solid tumors.

“If all goes well, we plan on being in the clinic this year,” he said of that particular program.

Marett said the company intends to take the momentum it has seen with its multiple co-development deals into J.P. Morgan as a potential means to gain additional funding to support its programs. He added that it will also be a good chance for BioNTech to meet with its co-development partners and “look at the state of the nation.”

https://www.biospace.com/article/biontech-teams-up-with-sanofi-to-target-solid-tumors-in-91-5-million-deal/

Six Things to Watch for at the JP Morgan Healthcare Conference

The JP Morgan Healthcare Conference, being held from January 7 through 10 at the Westin St. Francis Hotel in San Francisco, is one of the premier, possible the premier, conferences for the biopharmaceutical industry. Every year biotech, pharmaceutical and medical device company representatives and executives from around the world gather together with members of the investment community to network, cut deals, and provide updates on their pipelines.

In fact, it’s almost surprising that Bristol-Myers Squibb and Celgene didn’t wait a couple days to announce their pending $74 billion merger. Here are 6 stories to watch for.

#1. Moderna Therapeutics. After nabbing the record for largest initial public opening in December 2018, raking in $604.3 million dollars, the company’s chief executive officer, Stephane Bancel, is presenting an update on the company and its pipelines at the JP Morgan conference on Tuesday, January 8. Moderna’s always been good at raising money, even though it has no products on the market. But it currently has 21 programs in development, with 10 in the clinic and another three with open Investigational New Drug (INDs) submissions. Investors are undoubtedly going to be interested in what Moderna is doing with all that money and whether it can live up to the hype.

#2. Sarepta Therapeutics. On December 20, 2018, Sarepta completed the submission of its rolling New Drug Application (NDA) for accelerated approval for golodirsen (SRP-4053), a phosphorodiamidate morpholino oligomer engineered to treat Duchenne muscular dystrophy (DMD) in patients with genetic mutations subject to skipping exon 53 of the Duchenne gene. Sarepta, of course, is the company that brought the world the first treatment for DMD, Exondys 51, in 2016, after a controversial and dramatic year-long approval battle with (and within) the U.S. Food and Drug Administration (FDA). Management is presenting at JP Morgan on Monday, January 7 at 7:30 AM PST. Investors can expect an update on the golodirsen submission and likely questions about how Exondys 51 is doing in the marketplace as well as any follow-up clinical testing that is ongoing.

#3. Biogen. On January 4, Biogen announced it had signed a strategic collaboration deal with C4 Therapeutics to investigate C4T’s protein degradation platform to discover and develop therapies for neurological conditions like Alzheimer’s and Parkinson’s. Biogen is paying C4T up to $415 million in upfront and milestone payments, plus potential royalties. But it would be foolish to assume there won’t be updates and intense questioning about Biogen’s two ongoing Phase III clinical trials of aducanumab for Alzheimer’s disease, that it is developing with Eisai. Data from at least one of the trials is expected late this year. Biogen is presenting on Monday, January 7 at 3:30 PM PST.

#4. Gilead Sciences. Just a couple headlines about Gilead from 2018 tell the story: “Gilead—Down but Not Out?” and “Is Gilead Poised for a Comeback?” Gilead’s success is also its Achilles’ heel. The dominant player in the hepatitis C market, its drugs for HCV are so effective they are basically curing the disease. This results in a smaller and smaller patient pool to draw on. And pricing pressures and competitors are chipping away at the company’s dominance in the HCV market, but the biggest erosion is caused by its own success. Its HIV and Hepatitis B (HBV) products are strong, but whenever Gilead execs make presentations, there’s usually one big question that investors have: Will the company finally buy something meaningful? Gilead execs will participate in a fireside chat on Monday, January 7 at 9:30 A.M. PST.

#5. bluebird bio. Many investors are hoping bluebird bio will dazzle. It’s set up a number of interesting collaborations, including a deal with Gritstone Oncology in August 2018. Analysts expect the company to announce sales of $9.82 million for its current fiscal quarter. Its last quarterly earnings were posted on November 1, 2018. The company focuses on gene therapies for severe genetic diseases and cancer. Its product candidates are Lenti-D, which is in Phase II/III clinical trials for cerebral adrenoleukodystrophy, and LentiGlobin, for the treatment of transfusion-dependent beta-thalassemia and severe sickle cell disease. Company execs are presenting on Tuesday, January 8 at 2:30 P.M. PST. The company, with Celgene, is testing a therapy for multiple myeloma, and both companies have indicated they expect to file an application for the CAR-T treatment in 2020. As a result, late-stage trial data will be released sometime this year.

#6. The Player to be Named Later. There are almost always big surprises that come out of the annual JP Morgan conference—either big deals or surprisingly positive (or negative) pipeline news. One topic likely to be swirling around the conference is related to government proposals regarding drug pricing. Senator Elizabeth Warren (D-MA) recently announced the launch of presidential run shortly after proposing The Affordable Drug Manufacturing Act, which would allow Health and Human Services (HHS) to manufacture or contract out generic drug manufacturing, drug pricing will once again likely be a sizzling political talking point.

And a number of big pharma companies raised their drug prices this week. Allerganincreased more than two dozen drugs by almost 10 percent. Many of the drug prices were “relatively modest,” according to FOX Business, but some were “particularly high, including on some generics.”

Senator Ron Wyden (D-Ore.), ranking member of the Senate Finance Committee, proposed a bill, the Stopping the Pharmaceutical Industry from Keeping Drugs Expensive (SPIKE) Act, which has stalled in the Finance Committee. It would require pharma companies to justify price increases. Wyden has had a long and testy relationship with the drug industry, in particular with Pfizer.

Despite the Democrats taking control of the House, and Senator Chuck Grassley (R-Iowa)taking over leadership of the Senate Finance Committee, the bill may go nowhere. A spokesperson for Sen. Grassley told STAT, “As written, it sounds like it opens the door to price controls. Sen. Grassley opposes federal price controls on prescription drugs, which ultimately limit access for consumers and don’t work in the long-run to keep prices down.”

https://www.biospace.com/article/6-things-to-watch-for-at-the-jp-morgan-healthcare-conference/

BMS CEO Lays out Reasoning for $74 Billion Acquisition of Celgene

When Bristol-Myers Squibb announced that it was snapping up Celgene Corporation for $74 billion, the news sent shockwaves throughout the biopharma industry. There are numerous questions that have yet to be answered, and won’t be for some time, such as what will the new company look like and how many people could stand to lose their jobs due to the merger?

Over the past decade, BMS has been no stranger to flexing its M&A muscle. The company made numerous focused-acquisitions that have positioned itself as a leader in oncology. When announcing the acquisition, BMS CEO Giovanni Caforio noted that the massive deal for Celgene is another piece to that puzzle. Caforio said the combined might of the two pipelines will create “the number one oncology franchise” for both solid and hematologic tumors. The pillars of the combined pipeline will be built on the blockbuster checkpoint inhibitor Opdivo, as well as Yervoy and Celgene’s powerhouse drugs, Revlimid and Pomalyst. And, Caforio also pointed to a cardiovascular pipeline led by Eliquis and a pipeline of inflammation drugs helmed by Orencia and Otezla. As Carafio spoke, he described a bright future for the combined companies.

“Looking to the future, we are encouraged by the opportunities we have moving forward, including more than 20 near-term registrational readouts. We are also excited by the potential to move I/O (immuno-oncology) into early disease settings, develop PD-1 combinations with existing standards of care and address emerging I/O refractory second line,” Caforio said, according to a transcript of the conference call after the deal was announced. “All together, given the strength of our business and the opportunities that we see, I believe that we will continue to have a strong and leading I/O business into the future. Importantly, we will ensure that our commercial and R&D teams remain focused on delivering the value of this business.”

When Caforio spoke with investors and reporters Thursday, he pointed to certain indications where he sees future growth, particularly in the area of treatments for multiple myeloma. With the foundation set by Celgene’s Revlimid and Pomalyst, Carafio said they see the market evolving to one that includes new targets and modalities, such as BCMA, CELMoD and CAR-T. Carafio pointed to four near-term assets that have the potential to launch in the hematology market over the next one to two years. He said the combination of established and developmental products has strengthened the belief that the company will be “best positioned for long-term leadership in hematology.”

In addition to the potential launch of four hematology products over the next two years, the company is also expecting two launches in immunology and inflammation, with TYK2 and ozanimod.

“We believe these assets have the potential to generate greater than $15 billion in peak sales, while adding scale and breadth to our immunology and oncology franchises, as well as being the first step to the next stage in hematology leadership,” he said.

During the conference call, BMS did point to where it believes some $2.5 billion in savings can be found through cuts to R&D, manufacturing and other areas. Certainly, some cuts are expected in order to reduce redundancies, but how many jobs that will impact remains to be seen and likely won’t be fully realized for many months.

When those cuts are made, BMS Chief Financial Officer Charles Bancroft said the company will follow “guiding principles to ensure we retain talent, protect key value drivers and leverage the enhanced scale of the new company.”

https://www.biospace.com/article/bms-ceo-giovanni-caforio-lays-out-reasoning-for-74-billion-acquisition-of-celgene/