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/

Bristol-Myers downgraded to Hold from Buy at Edward Jones

https://thefly.com/landingPageNews.php?id=2843907

Celgene raised Revlimid price effective January 3

On the same day Celgene (CELG) announced its proposed takeover by Bristol-Myers (BMY), the company was also hiking the price of its blockbuster cancer drug, Bloomberg reports. Celgene raised the price of a 10-milligram dose of Revlimid by 3.5% to $719.82 effective January 3, the report says, citing price data compiled by Bloomberg Intelligence and First Databank. The biotechnology company also hiked the price of psoriasis therapy Otezla, the cancer treatment Abraxane, and two other drugs by the same percentage, the report notes. Celgene spokesman Greg Geissman said the 3.5% raise is lower than the expected rate of spending growth in U.S. health care, according to Bloomberg
https://thefly.com/landingPageNews.php?id=2843971

Ironwood names Mark Mallon CEO

Ironwood Pharmaceuticals (IRWD) announced that the Ironwood board of directors has appointed CEOs of the two companies, effective at the time of Ironwood’s planned separation which is on track to be completed in 1H19. Industry veteran Mark Mallon will become CEO and a director of Ironwood. Mallon is joining Ironwood effective immediately as executive senior advisor, working closely with Peter Hecht, founding CEO of Ironwood, through the separation. Peter Hecht will become CEO and a director of Cyclerion Therapeutics, the soluble guanylate cyclase biotechnology business focused on the development of five sGC stimulators targeting the treatment of serious and orphan diseases. Mallon joins Ironwood following a distinguished 24-year career at AstraZeneca (AZN) where he held a variety of senior executive positions. He most recently served as a member of its executive committee, reporting to the CEO, as executive vice president of global product and portfolio strategy leading global marketing, commercial operations, pricing and market access, medical affairs and corporate affairs for AstraZeneca’s $18B pharmaceutical business. Peter Hecht has served as Ironwood’s CEO and director since co-founding the company in 1998. Ironwood is on track to complete the separation in the first half of 2019, subject to customary conditions, including a favorable opinion with respect to the tax-free nature of the transaction, and final approval of Ironwood’s board of directors.
https://thefly.com/landingPageNews.php?id=2843983