Biogen bolsters pipeline again with Alectos deal

 Biogen has added a preclinical-stage drug candidate for Parkinson’s disease via a $722.5 million licensing agreement with Alectos Therapeutic, as it continues to rebuild a pipeline behind its side-lined Alzheimer’s therapy Aduhelm.

The deal includes a $15 million upfront payment that gives Biogen global rights to selective GBA2 inhibitor AL01811, which it says has the potential to become a first-in-class oral therapy for Parkinson’s that could strike at the pathological mechanisms that underlie the neurodegenerative disease.

In a statement, Biogen said that AL01811 is designed to target dysfunction in lysosomes – organelles which play a vital role in cell function by breaking down excess or worn-out cell parts and can be impaired in Parkinson’s.

Alectos’ drug helps to maintain the acid pH level in lysosomes required for their function in the hope of restoring their activity and – hypothetically at least – slow the progression of Parkinson’s in patients with and without known genetic risks.

Along with the upfront payment, Biogen has pledged up to $77.5 million in potential development payments, as well as up to $630M in commercial milestones if AL01811 makes it to market and performs as hoped.

People who have Parkinson’s experience numerous symptoms, including tremors, slow movement, muscle stiffness and impaired balance. As these symptoms become progressively worse, patients have difficulty walking, talking or completing other simple tasks.

Parkinson’s is the second most common neurodegenerative disease, and there are no approved therapies capable of slowing progression, with current therapies aimed at bolstering levels of dopamine, a neurotransmitter that becomes depleted in the disease.

Biogen and Alectos will collaborate on the remaining preclinical work on AL01811, with Biogen taking responsibility for the project if it reaches the clinical testing stage.

It’s not the first time that Biogen has licensed rights to a drug targeting lysosomal function in Parkinson’s disease.

In a deal signed in 2020, the biotech bought a licence to co-develop and co-market inhibitors of LRRK2 – another target linked to lysosome function – from Denali Therapeutics.

That much larger agreement covered multiple compounds and included a $560 million upfront payment, a $465 million equity investment and up to $1.125 billion in potential milestone payments.

The first clinical compound from the alliance – BIIB122 – is in a phase 3 study called LIGHTHOUSE in Parkinson’s with and without LRRK mutations, and has just started the phase 2b LUMA trial in patients with early-stage disease.

While a long-term play, the new agreement is a further sign of Biogen’s efforts to rebuild its pipeline after admitting that Aduhelm (aducanumab) will not make any commercial contribution anytime soon, and other setbacks such as the failure of two Ionis-partnered  amyotrophic lateral sclerosis (ALS) in the last few months and a tau antibody for Alzheimer’s disease.

Recent deals include a $3 billion buy into Sage’s novel antidepressant zuranolone, plus smaller collaborative deals with InnoCare in multiple sclerosis, TMS in ischaemic stroke and gene therapy specialist Capsigen.

https://pharmaphorum.com/news/biogen-bolsters-pipeline-again-with-alectos-deal/

Halozyme Launches TLANDO Oral Treatment for Testosterone Replacement

 -Halozyme Therapeutics, Inc.,  (NASDAQ: HALO) ("Halozyme") today announced the commercial launch of TLANDO™ (testosterone undecanoate), an oral treatment indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadotropic hypogonadism). TLANDO™ was approved by the U.S. Food and Drug Administration (FDA) on March 28, 2022.

https://www.biospace.com/article/releases/halozyme-announces-commercial-launch-of-tlando-an-oral-treatment-for-testosterone-replacement-therapy/

JanOne Issued U.S. Patent Covering Method of Improving Nerve Function

 JanOne Inc. (Nasdaq: JAN), a company that focuses on the development of drugs with non-addictive, pain-relieving properties, announced today that a patent was issued that covers a method of improving nerve function using JAN101. JAN101 (formerly known as TV1001SR), is a potential treatment for peripheral artery disease (PAD), a vascular disease that affects more than 8.5 million people in the U.S. and more than 60 million people worldwide.

"This patent further protects JanOne Inc.'s product for use in treating PAD by extending the use of JAN101 to treat the nerve damage caused by microvascular disease," said Dr. Tony Giordano, JanOne Inc.'s Chief Scientific Officer. "Microvascular disease is a major problem for PAD patients: it leads to restricted blood flow in the affected limb, which in turn leads to nerve damage and severe pain.  Recent studies have in fact suggested that PAD is a microvascular disease, so the observation that JAN101 improves microvascular and nerve function is crucial in treating this disease."

Dr. Amol Soin, a leading pain physician and JanOne's Chief Medical Officer, added, "We believe that nerve damage plays a major role in promoting pain and thus studied whether JAN101 could improve nerve sensory velocity and nerve sensory conductance in a previous trial I oversaw.  Our previous studies showed that JAN101 improved nerve conduction velocity, which leads us to believe that it may not only improve pain but could also improve nerve function."

This method for treating pain was co-discovered by Dr. Christopher Kevil, Vice Chancellor for Research and Dean of the School of Graduate Studies at LSU Health Shreveport. This newly approved patent is owned by LSU Health Shreveport and is exclusively licensed to JanOne Inc. It is the latest United States patent to be issued in connection with JanOne's Inc.'s PAD and pain development program.

https://www.biospace.com/article/releases/janone-inc-announces-the-issuance-of-u-s-patent-covering-a-method-of-improving-nerve-function-using-jan101/

Seres Touts Strong Phase III Results Against Recurrent C. Difficile Infection

 Massachusetts-based Seres Therapeutics, Inc. announced Tuesday that its Phase III Ecospor IV study demonstrated a strong safety profile in addition to statistically significant positive results. The study uses an open-label design to determine the potential of SER-109, a potentially first-in-class microbiome therapeutic to treat recurrent C. difficile infection (rCDI).

The study is placebo-controlled, double-blinded and randomized. The primary outcome measurement focuses on the participants’ infection recurrence after treatment for eight weeks. Infection is confirmed using a toxin assay. Secondary outcome measures evaluate recurrence rates at the 4, 12 and 24-month marks within each treatment group. Additional measurements look at the time to infection recurrence and tolerability of the treatment.

SER-109 is an orally delivered therapeutic that provides purified firmicutes to the patient’s microbiome to prevent C. difficile colonies from forming. Firmicutes are a classification of bacteria that are critical to gut health, which in turn, plays a significant role in overall metabolic function. The candidate’s unique mechanism influenced the U.S. Food and Drug Administration’s (FDA) decision to grant Breakthrough Therapy and Orphan Drug designations for SER-109 when indicated to treat rCDI.

President and Chief Executive Officer at Seres, Eric Shaff commented on the results.

“The Ecospor IV data confirm the well-tolerated safety profile and clinical benefit observed in the prior Ecospor III study,” he said. “These results, along with the start of the rolling BLA submission, significantly advance our ability to deliver what may be the first FDA-approved microbiome therapeutic. We believe that SER-109 has the potential to fundamentally transform the management of rCDI across all 170,000 annual cases in the U.S. and are working closely with Aimmune Therapeutics, a Nestlé Health Science Company, to bring this therapeutic candidate to patients as quickly as possible.”

According to Mayo Clinic, recent antibiotic use is not necessary for suspecting a diagnosis of rCDI. However, if antibiotic use is the culprit, that particular antibiotic regimen must be stopped. Other antibiotics might be prescribed to remedy the damage caused and clear up the infection, such as vancomycin, fidaxomicin and/or metronidazole.

Mayo Clinic goes on to explain that a quarter of infected persons experience recurrence, with the risk of recurrence multiplying each time. After contracting three infections, over 50% of patients will have to battle the infection once again. Patients most likely to fall victim to rCDI are over the age of 65, have an underlying gastroenterological medical condition or are simultaneously being treated for two conditions with antibiotics.

Non-traditional treatments, such as fecal microbiota transplant or human antibody treatments, are available to combat rCDI under physician discretion. No treatments are commercially available that use a microbiome supplementation mechanism. Similar candidates are in preclinical studies, including mitochondrial therapeutics and bacterial consortiums, along with microbiota competitors that have reached Phase III clinical trials.

https://www.biospace.com/article/seres-announces-strong-phase-iii-results-against-recurrent-c-difficile-infection/

Merck Predicts Over 80 Potential Oncology Approvals Through 2028

 Powered by its blockbuster checkpoint inhibitor Keytruda, Merck is forecasting the potential of more than 80 new regulatory approvals in oncology through 2028.

Merck showcased its oncology pipeline at the American Society of Clinical Oncology meeting in Chicago. The company presented data from nearly 120 abstracts in more than 25 cancer types. Over the past decade, Merck’s oncology pipeline has exploded, driven by Keytruda, which is predicted to become the world’s top-selling drug after AbbVie’s Humira loses patent protection next year.

At the ASCO presentation, Dean Y. Li, president of Merck Research Laboratories, reminded us that it’s only been a decade since Phase I data for the drug that would become Keytruda was first presented.

“Since that time, we have created a broad portfolio of oncology medicines with indications in 22 tumor types and have helped usher in a new era of cancer treatment – and most importantly, have helped patients all around the world. With our expansive portfolio and pipeline, we are continuing to help transform care for patients with cancer and hope to receive more than 80 approvals through 2028,” Li said in a statement.

The company highlighted more than 20 investigational candidates targeting multiple aspects of cancer cell biology and immune-based pathways across four distinct research areas. For immuno-oncology, Merck pointed to three ongoing Phase III programs assessing favezelimab, an anti-LAG-3 antibody; quavonlimab, an anti-CTLA-4 antibody; and vibostolimab, an anti-TIGIT antibody. Each of these is being assessed in combination with Keytruda. Also in this space, Merck is developing an anti-ILT-4 antibody, an anti-ILT-3 therapy, and a selective IL-2 agonist.

Antibody-drug conjugates are also being explored by Merck. The company has multiple programs in development, including the Phase III zilovertamab vedotin being assessed in tumors that express elevated levels of receptor tyrosine kinase-like orphan receptor 1. Another ADC in development in collaboration with Seagen is ladiratuzumab vedotin, which is designed to target tumors expressing LIV-1, a zinc transporter protein.

The company is also developing cell-based therapies and T-cell and NK cell engagers for the treatment of different forms of cancer. Merck said that in collaboration with Dragonfly Therapeutics and Janux Therapeutics, it is assessing bi- and tri-specific NK and T-cell engagers. The company is also evaluating allogeneic cell therapies through our collaborations with Artiva and A2 Biotherapeutics.

The fourth area of research is molecularly targeted therapeutics. The company noted that Welireg, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor that was approved last year for the treatment of certain von Hippel Lindau-associated tumors, is being studied in multiple settings, including renal cell carcinoma.

Merck is also developing nemtabrutinib, a selective, oral, reversible non-covalent Bruton’s tyrosine kinase inhibitor, and a small molecule KRAS G12C inhibitor for the treatment of hematological cancers and solid tumors, respectively. Through its 2020 collaboration with Seagen, the company is also studying Tukysa, a tyrone kinase inhibitor, for the treatment of HER2-positive cancers.

Outside of oncology, Merck posted new post-hoc data for its antiviral drug Lagervio (molnupiravir) that showed a lower proportion of COVID-19 trial participants who were treated with the medication required an acute care visit. Fewer patients needed respiratory interventions, the company noted.

Lagevrio received Emergency Use Authorization from the FDA at the end of 2021. It was greenlit for the treatment of mild to moderate COVID-19 infections in adults who are at high risk of progression to severe disease. However, due to some efficacy issues, the FDA EUA limited use of the medication to situations where other treatment options for COVID-19 are not available or clinically appropriate,

The data announced this morning from the Phase III Move-Out study, which assessed the medication in non-hospitalized adults with mild to moderate COVID-19, showed that only 7.2% of patients who received the antiviral required an acute care visit. That was in comparison to 10.6% of placebo patients. Additionally, for those who did require hospitalization, Merck noted that trial data showed patients who received Lagevrio required a shorter stay than those in the placebo group, or nine days compared to 12.

“The analyses add to our understanding of the clinical profile of Lagevrio and help to reinforce the importance of Lagevrio as part of the response to the COVID-19 pandemic,” Li said in a statement.

Lagevrio is also being assessed in a Phase III trial as a prophylaxis treatment for COVID-19.

https://www.biospace.com/article/ambitious-merck-expects-over-80-approvals-through-2028/

Mirati Therapeutics Is Angling To Rival Amgen — And Could Succeed

 Shares of MRTX stock rocketed Tuesday after Mirati Therapeutics (MRTX) unveiled early — but promising — test results for a lung cancer treatment.

In morning trades on today's stock market, MRTX stock rocketed 22% near 52.70.

Mirati added its treatment, adagrasib, to Merck's Keytruda in patients with a form of lung cancer. Early evidence suggested patients responded to the combination and, importantly, there were few elevations in liver enzymes.

The latter point is particularly important. Mirati's drug targets cancer in patients with a mutation known as G12C in their KRAS gene, a gene tied to cancer. Merck's (MRK) Keytruda is a checkpoint inhibitor. Researchers had believed combining these drug classes would cause liver damage. So physicians often pair checkpoint inhibitors instead with chemotherapy and its deluge of body-battering side effects.

"While the data presented thus far are immature and largely unconfirmed, we are encouraged that the adagrasib and Keytruda regimen appears tolerable and may offer a chemo-free option for the (previously untreated patients)," SVB Securities analyst Andrew Berens said in a report to clients.

MRTX Stock: Rivaling Amgen In KRAS

With this drug, Mirati is looking to rival Amgen (AMGN). Amgen sells Lumakras, another treatment for lung cancer tied to the G12C mutation in the KRAS gene. Lumakras is approved as a sole agent, but Amgen is testing the drug in combination with Keytruda for lung cancer. Amgen stock fell a fraction near 243.70.

Amgen's data, however, are "largely expected to be disappointing," Berens said. So, Mirati's fresh data release "could now be seen as an opportunity for Mirati."

The test results are very early, however. In one study, researchers could evaluate just six patients. Of those, four responded to the treatment. A second study of nine patients saw seven respond. At the median, patients are still responding after just over two months.

"Key takeaways suggest that this is a tolerable chemo-free regimen that could be at least as (effective) as checkpoint inhibitor regimens," Berens said. He has an outperform rating on MRTX stock.

Eliminating Chemotherapy

Importantly, elevations in liver enzymes were in line with adagrasib as a sole therapy, Berens said.

Eliminating chemotherapy from the treatment paradigm has benefits for patients. Chemo is harsh on the body. Think of it like a hammer, rather than a laser — it smashes everything in its path, not just the cancer. This often causes systemic problems for patients.

The results helped MRTX stock reverse a dip Monday as investors digested another test of adagrasib. That study examined the drug's potential as a sole treatment in patients with lung cancer. Then, analysts questioned whether adagrasib would differentiate itself from Amgen's Lumakras.

https://www.investors.com/news/technology/mrtx-stock-surges-on-the-surprising-way-it-could-rival-amgen-and-win/

8 of 10 Patients Maintained Skin Clearance at One Year in Lilly Atopic Dermatitis Monotherapy Trials

 Eli Lilly and Company (NYSE: LLY) today announced topline results from one-year analyses of the efficacy and safety of lebrikizumab, the company's investigational IL-13 inhibitor for the treatment of patients with moderate-to-severe atopic dermatitis (AD). The new findings from the Phase 3 clinical trials (ADvocate 1 and 2) showed eight out of ten patients who achieved clinical response (EASI-75*) with lebrikizumab monotherapy at 16 weeks maintained skin clearance at one year of treatment with the once every two weeks or four weeks regimen. Additionally, patients treated with lebrikizumab maintained itch relief across the two trials over the one-year period. These results build upon positive data from the 16-week, double-blind, placebo-controlled part of the ADvocate program.

https://finance.yahoo.com/news/eight-ten-patients-maintained-skin-040100283.html