Spero Therapeutics, Gates Foundation Collaborate on Tuberculosis Treatment

Cambridge, Mass.-based Spero Therapeutics and the Bill & Melinda Gates Foundation have teamed up to take on the challenge of a lung infection that has been designated as a critical concern by the World Health Organization.

Spero and the Gates Foundation will work together to tackle lung infections caused by Mycobacterium tuberculosis (Mtb). The organizations will develop Spero’s antimicrobial agent SPR720, which Spero has been developing for the treatment of rare non-tuberculous mycobacterial (NTM) infections. NTMs are ubiquitous environmental pathogens that can cause progressive lung damage and respiratory failure, particularly in patients with compromised immune systems or underlying pulmonary disorders. Although rare, the incidence of pulmonary NTM infections is increasing worldwide.

Preclinical studies have demonstrated the potency of SPR720 against clinically important mycobacteria, including three NTM species — Mycobacterium avium complex and Mycobacterium abscessus, as well as Mycobacterium tuberculosis, Spero said in its announcement. The company said the collective data suggest that SPR720 has an acceptable safety profile and encouraging target pathogen efficacy.

SPR720 is currently being evaluated in a double-blind, placebo-controlled Phase I clinical trial to assess the safety, tolerability and pharmacokinetics of SPR720 in healthy volunteers. Spero anticipates top-line data from the Phase I clinical trial by the end of 2019. There are currently no oral antibiotics specifically approved for use to treat pulmonary NTM infections. If successfully developed, SPR720 has the potential to address an important unmet need as the first oral antibiotic. SPR720 has been granted Qualified Infectious Disease Product designation from the U.S. Food and Drug Administration for the treatment of lung infections caused by non-tuberculous mycobacteria and lung infections caused by Mycobacterium tuberculosis.

Spero Chief Executive Officer Ankit Mahadevia said they are excited about the prospects of SPR720 for the treatment of NTM. This development will allow the medication to meet the challenges of an important unmet need in the treatment of tuberculosis around the world. Mahadevia added that the company is excited about working with Gates MRI to address the “current public health crisis” in tuberculosis in low- and middle-income countries around the world.

“Spero will benefit from the significant development and industry experience that the Gates MRI team can offer as well as synergies between the TB and NTM development paths as SPR720 progresses through clinical trials,” Mahadevia said in a statement.

Under terms of the deal, Spero granted the Bill & Melinda Gates Medical Research Institute (Gates MRI) an exclusive license to develop, manufacture and commercialize SPR720 for the treatment of tuberculosis (TB) in low- and middle-income countries. Gates MRI will conduct and fund preclinical and clinical studies for the development of SPR720 against TB. Additionally, Gates MRI will fund certain collaborative to support Gates MRI’s charitable purposes. To enable the collaboration with Gates MRI, Spero said it reached an agreement with Vertex, the company that developed SPR720.

Penny Heaton, CEO of Gates MRI, touted the deal with Spero. She said they see SPR720 as a “potential new tool to meaningfully address tuberculosis, the leading causing of death from infectious disease in the world.”

https://www.biospace.com/article/spero-therapeutics-and-the-gates-foundation-collaborate-on-tuberculosis-treatment/

Strength of Oncology Pipeline Touted at Merck’s First Investor Day in Five Years

During an investors’ day conference on Thursday morning, Merck Chief Commercial Officer Frank Clyburn pointed to the growth opportunities ahead of the company in oncology due to the strength of three medications. Merck has the potential to see regulatory approval for more than 50 additional indications in oncology over the next five years for Keytruda, Lynparza and Lenvima. Over the next decade, Mike Nally, Merck’s chief marketing officer, said the company will be the leader in oncology due to its efforts in this field. Nally said the company has the largest immuno-oncology pipeline in the industry and only sees that leading to the company’s continued leadership in this area.

Ahead of the investors’ day, the first in five years for the company, there were some analysts who expressed concern over the company’s reliance on Keytruda. However, from the presentations this morning, it’s clear that Keytruda will remain a tent pole medication for the company for the foreseeable future. Six years after it was launched, Keytruda is one of the best-selling drugs in the world. Last year, it generated more than $7 billion in revenue and that is only predicted to grow, particularly as the drug wins approval for new indications. Over the next five years, Clyburn said Keytruda’s approved indications are expected to more than double with approvals as part of new combinations and in different stages of therapy, including adjuvant and neoadjuvant. Keytruda recently picked up two new approvals from the FDA. And, more are expected to come.

During the presentation, Clyburn said there are significant growth opportunities for Keytruda in multiple cancers. He said Keytruda is a “significant cornerstone” for long-term growth at Merck.

“In a short time, Keytruda has become a foundational cancer treatment. We have activity across 25 different cancer types… and Keytruda is changing the way in which patients are being treated today,” Clyburn said.

Roy Baynes, Merck’s head of global clinical development, concurred with Clyburn. He said Keytruda is still in the early stages of development and is part of more than 1,000 clinical trials. With the ongoing trials, Baynes said the company is building a “wall of data” around Keytruda.

Lynparza, the PARP inhibitor co-developed with AstraZeneca, and Lenvima are also expected to be strong contributors to the company’s oncology future. With Lynparza, Clyburn said there are growth opportunities across multiple tumor types. He noted that Lynparza has class leadership in the U.S., with nearly 60% of total PARPi prescriptions. Following strong Phase III results in pancreatic cancer, the first time a PARP inhibitor demonstrated activity in germline BRCA-mutated metastatic pancreatic cancer, Merck and AstraZeneca plan to seek regulatory approval. With Lenvima, a multiple receptor tyrosine kinase inhibitor approved for renal cell carcinoma and hepatocellular carcinoma (HCC), Merck sees significant growth opportunities in China, where HCC is prevalent.

Merck’s vaccine business is also a key to growth. Clyburn said global leaders keep telling him are essential to answering ongoing health concerns across the world. Since 2010, Merck has doubled its vaccine business and Clyburn said it will continue to grow. One of the key drugs in its vaccine portfolio is Gardasil, a treatment for human papillomavirus. Gardasil is seeing increased growth driven by global appeals to eliminate cervical cancer. Less than 3% of the world has received an HPV vaccine, so Merck sees significant opportunities for growth there, Clyburn said.

HIV treatments are also key to future growth at Merck. Last year, the company won approval for two new HIV treatments, Delstrigo, a once-per-day triple combination treatment, and Pifeltro, a new non-nucleoside reverse transcriptase inhibitor. Merck also has a promising clinical candidate that could be a game changer in HIV treatment. Nally pointed to MK8591 as a future backbone treatment for HIV due to its efficacy and long half-life that could allow for weekly, or even monthly dosing.

“This compound has a real potential to fundamentally change the transmission dynamics of HIV patients,” Nally said.

Merck Chief Executive Officer Ken Frazier touted Merck’s team and its abilities to deliver potent therapies to patients across multiple diseases. He called it a team sport to bring a drug through the clinic and to market. He said Merck has a strong team to “do this on a repeated basis.”  He pointed to the company’s desire to “follow the science,” which not only transforms treatment options but also the company as well. Since Merck’s last investor day held five years ago, he said no one thought of Merck as an oncology company. But thanks to Keytruda, Merck is a “leader in immuno-oncology because they have been willing to evolve depending on where the science took us.”

https://www.biospace.com/article/strength-of-keytruda-touted-at-merck-s-first-investor-day-in-five-years/

466 Jobs to Be Cut in France and Germany Amid Sanofi’s R&D Revamp

Paris-based Sanofi announced that it plans to restructure its research and development (R&D) operations in Germany and France, which will result in the loss of 466 jobs in the two countries. The intention is to focus its research efforts on cancer, immunology, rare diseases and vaccines.

Sanofi plans to halt new research in cardiology indications but keep existing research programs. It also plans to refocus its diabetes research on the root causes of the disease, but continue developing its current diabetes pipeline.

The job cuts will be on a voluntary basis.

Sanofi has typically had a reputation for using collaborations for innovation, instead of focusing on in-house innovation. Its most notable partnership is with Regeneron, but the company downgraded that relationship in January.

In the spring of 2018, Sanofi brought on former Roche research head John Reed to replace retiring Elis Zerhouni. In the year before Reed took over, the company was working to shift toward more internal R&D, with a goal of developing more in-house compounds.

Despite that, shortly after Reed took over, he oversaw a collaboration deal with Denali Therapeutics for $125 million upfront and possible milestones that could exceed $1 billion. The two companies are working to develop DNL747 and DNL758 for inflammatory diseases like rheumatoid arthritis and psoriasis (DNL758) and multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis (DNL747).

Reed stated that the recent restructuring is a way to shift money to other therapeutic areas. It expects to increase its immuno-oncology and gene therapy research in France and invest more on gene therapy R&D research in the U.S. In Germany, it expects to invest more in antibody engineering.

“The transformation of our R&D organization would enable us to focus on the therapeutic areas and platforms where we believe we have the greatest opportunity to make a meaningful difference for patients and to maximize the productivity of our research engine,” Reed stated.

As part of its efforts to develop more projects internally, the company announced on June 17 that it was restructuring its relationship with Voyager Therapeutics. The original deal was inked in 2015. Under the new terms of the deal, Voyager received worldwide rights to the VY-HTT01 Huntington’s disease program and rights outside the U.S. to the VY-FXN01 Friedreich’s ataxia program. The ex-U.S. rights to VY-FXN-1 were then transferred from Voyager to Neurocrine Biosciences under a deal Voyager and Neurocrine announced in January.

Sanofi Genzyme also picked up exclusive option rights to specific novel AAV capsids that Voyager owns or controls. These will be for exclusive use for up to two non-central nervous system indications.

As part of that restructuring, Voyager paid Sanofi Genzyme $10 million upfront, partially offset by $5 million from Neurocrine to Voyager over the VY-FXN01 rights shift. Voyager will also pay another $10 million in milestones to Sanofi Genzyme once it files an investigational new drug (IND) application for VY-HTT01 or, if it applies, to some backup compounds for Huntington’s disease.

Other programs that ended between Voyager and Sanofi include Sanofi Genzyme’s option to acquire rights to a future Voyager CNS orphan program and a spinal muscular atrophy (SMA) program, where the intellectual property rights are returned or exclusively licensed to Sanofi Genzyme.

https://www.biospace.com/article/sanofi-to-restructure-r-and-d-in-germany-and-france-cut-466-jobs/

Ventas upped to buy from Hold by Stifel

Target to $74 from $65

https://www.benzinga.com/stock/VTR/ratings

Novo Nordisk cut to Hold from Buy by Deutsche Bank

https://www.benzinga.com/stock/NVO/ratings

Joint Corp. started at Buy by B. Riley

Target $23

https://www.benzinga.com/stock/JYNT/ratings

Genomic Health upgraded to Overweight from Neutral by Piper

Target $72

https://www.benzinga.com/stock/GHDX/ratings