Eiger Biopharmaceuticals Files for Chapter 11

  Eiger Biopharmaceuticals Inc., a company developing therapies for rare metabolic diseases, has filed for bankruptcy.

Publicly traded Eiger listed about $38.8 million in assets and $53.1 million in liabilities in a Chapter 11 petition filed Monday in Dallas. The bankruptcy filing will give Eiger time to discuss restructuring options with its creditors.

The stock fell as much as 51% after Bloomberg reported the filing. In bankruptcy, equity is last in line for repayment and shareholders are usually wiped out.

Eiger, based in Palo Alto, California, filed Chapter 11 after its board of directors explored other financing options including searching for equity financing, according to court documents. The company said it develops therapies for hepatitis delta virus and other serious diseases.

Eiger said in court papers it will attempt to sell its assets in Chapter 11.

https://finance.yahoo.com/news/eiger-biopharmaceuticals-files-chapter-11-142653525.html

Disc Medicine Plummets 59% After Placebo Effect Confounds Sunlight Sensitivity Study

 Disc Medicine's (IRON) light sensitivity treatment succeeded in a midstage study Monday, but an outsized placebo response confounded the results and the biotech stock plummeted.

The biotech company is trying to treat erythropoietic protoporphyria, a rare condition in which a toxic substance called protoporphyrin IX builds up in the blood. Patients experience severe reactions in the sunlight, including pain, swelling, burning sensations, blistering and disfigurement.

After 17 weeks, patients who received Disc's drug, bitopertin, had statistically significant reductions in protoporphyrin IX.

But the secondary goal of the study — time spent in the sunlight without pain — wasn't statistically significant due to a "greater than expected" response from the placebo group, Disc said in a news release. On average, low-dose and high-dose patients spent 175.1 hours and 153.1 hours in the sunlight without pain, respectively. Placebo patients reached 133.9 hours.

In premarket trades on today's stock market, Disc stock crashed 59.4% to 25.30. 

https://www.investors.com/news/technology/biotech-stock-disc-medicine-light-sensitivity-aurora-study/

Akari merger and year end update

 Akari announced the company has reached a definitive agreement with Peak Bio Inc. (Peak Bio) to merge as equals in an all-stock transaction. The combined entity will operate as Akari Therapeutics, Plc, which is expected to continue to be listed and trade on the Nasdaq Capital Market as AKTX.

Following closing, the company will have an expanded pipeline that contains multiple compelling assets spanning early and late development stages, including: a robust antibody drug conjugate (ADC) toolkit with novel payload and linker technologies, a Phase 2-ready neutrophil elastase inhibitor (NEI) program targeting alpha-1 antitrypsin deficiency (AATD), nomacopan, a bispecific inhibitor of two immune pathways (complement C5 and leukotriene B4/LTB4) in Phase 3 development for pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA), and long-acting PAS-nomacopan for geographic atrophy (GA).

A strategic assessment of the pipeline is planned to evaluate development of the four programs including program prioritization, updated timelines, near-term value creation opportunities, and other considerations. The assessment is expected to be complete prior to the closing of the merger.

The Phase 3 Part A clinical trial of investigational nomacopan in pediatric HSCT-TMA is studying multiple age groups with a focus on PK/PD and dose confirmation. Akari is continuing to recruit patients into the Part A portion of the Phase 3 clinical trial that has treated 10 patients to date. Enrollment in Part A is guided by new consensus criteria published in 2023 supporting earlier screening and diagnosis of high-risk (severe) patients with HSCT-TMA. The Phase 3 clinical trial also is expected to include a Part B portion focusing on safety and efficacy. Plans for initiation of the Part B study will be guided by the strategic pipeline assessment.

HSCT-TMA is a rare complication of stem cell transplant that has no approved treatment options and an 80% mortality rate among severe patients. Nomacopan is in development as potentially the first treatment approved for the condition.

Akari was granted orphan drug designation from the European Commission for treatment in hematopoietic stem cell transplantation, and FDA Orphan Drug, Fast Track and Rare Pediatric Disease designations for nomacopan for the treatment of pediatric HSCT-TMA. With the FDA Rare Pediatric Disease Designation, Akari is eligible to receive a Priority Review Voucher (PRV) upon approval of nomacopan that it can either redeem for priority review of a subsequent marketing application for a different product or sell to a third party. 

During 2023, Akari also advanced the long-acting version of nomacopan (PASylated nomacopan) into the final stages of pre-clinical development as a treatment for geographic atrophy (GA). PAS-nomacopan is being developed with the potential to address significant unmet patient needs, including a longer dose interval between intravitreal injections and reduction of choroidal neovascularization (CNV) risk associated with approved complement-only inhibitors currently used for treatment of GA. Positive pre-clinical results, including an advanced high-yielding manufacturing process that provides a drug with specifications considered suitable for intravitreal administration, support the potential initiation of clinical development with Phase 1 single and multiple ascending dose (SAD/MAD) testing to evaluate safety and pharmacokinetics/ pharmacodynamics (PK/PD). A progressive and sight-threatening condition, GA is estimated to affect 5 million people worldwide, including 1 million patients in the U.S.

Full-Year 2023 Financial Results

As of December 31, 2023, the company had cash of approximately $3.8 million. In March 2024, the company received approximately $2.0 million in gross proceeds from certain existing investors from the sale of ADSs in a private placement and is planning to secure additional capital in the second quarter of 2024.

Research and development expenses were approximately $5.5 million for the year ended December 31, 2023, as compared to approximately $9.6 million for the same period in 2022.

General and administrative expenses were approximately $11.4 million for the year ended December 31, 2023, as compared to approximately $13.5 million for the same period in 2022.

Total other income, net was approximately $6.8 million for the year ended December 31, 2023, as compared to approximately $5.3 million for the same period in 2022, of which $6.6 million and $5.0 million (net) was the result of net non-cash gains related to the company's liability-classified warrants issued in connection with the company's September 2022 private placement transaction.

Net loss was approximately $10.0 million for the year ended December 31, 2023, as compared to net loss of approximately $17.7 million for the same period in 2022. Excluding the net non-cash gains of approximately $6.6 million and $5.0 million (net) for the years ended December 31, 2023 and 2022, respectively, related to the company's liability-classified warrants, net loss was $16.6 million and $22.7 million, respectively.

https://www.globenewswire.com/news-release/2024/04/01/2855059/0/en/Akari-Therapeutics-Reports-Full-Year-2023-Financial-Results-and-Recent-Highlights.html

Sunshine Biopharma Results

 Sunshine Biopharma Inc. (NASDAQ:SBFM) (the "Company"), a pharmaceutical company offering and researching life-saving medicines in a variety of therapeutic areas including oncology and antivirals today announced that it has filed its 2023 financial results on Form 10-K on Thursday March 28, 2024. The following are highlights of the report:

• Sales in 2023 grew to a total of $24,092,787, primarily as a result of a full year of revenues generated by the acquisition of Nora Pharma in October 2022. Nora Pharma's revenues for its fiscal year ended June 30, 2022, were $10,766,982.
• The average 2023 quarter-over-quarter growth rate in sales was 14%.
• Loss per share decreased from a negative $1.76 per share in 2022 to a negative $0.19 per share in 2023, predominantly due to a one-time write-off of goodwill in 2022.
• Completed a private placement of approximately $5 million in gross proceeds for use in part for expansion of sales operations.
• Repurchased 513,723 shares of the Company's common stock on the market for a total of $541,143.
• The Company's two proprietary drugs in development advanced to the animal testing stage for both SBFM-PL4 targeted for SARS Coronavirus infections and K1.1 mRNA for liver cancer.
• IND-enabling studies of Adva-27a anticancer compound were halted in November 2023 pending further analysis of unfavorable in vitro results obtained earlier in the year.

"We are happy with our 2023 results, as we continue to strive to achieve profitability," said Dr. Steve Slilaty, CEO of Sunshine Biopharma. "We look forward to further growth in 2024 and beyond as we expand our operations and bring more life-saving drugs to market," he added.

https://www.accesswire.com/848518/sunshine-biopharma-reports-operating-results-for-the-fiscal-year-ended-december-31-2023

Russian military intelligence unit may be linked to 'Havana syndrome': reports

 The mysterious "Havana syndrome" ailment that has afflicted U.S. diplomats and spies across the world may be linked to energy weapons wielded by members of a Russian military intelligence sabotage unit, the Insider media group reported.

A U.S. intelligence investigation whose findings were released last year found that it was "very unlikely" a foreign adversary was responsible for the ailment, first reported by U.S. embassy officials in the Cuban capital Havana in 2016.

But Insider, a Russia-focused investigative media group based in Riga, Latvia reported that members of a Russian military intelligence (GRU) unit known as 29155 had been placed at the scene of reported health incidents involving U.S. personnel.

The year-long Insider investigation in collaboration with 60 Minutes and Germany's Der Spiegel also reported that senior members of Unit 29155 received awards and promotions for work related to the development of "non-lethal acoustic weapons".

Russia has previously denied any involvement.

Symptoms of the ailment have included migraines, nausea, memory lapses and dizziness.

The Insider report said the first incident of "Havana Syndrome" symptoms may have happened earlier than 2016.

It said "there were likely attacks two years earlier in Frankfurt, Germany, when a U.S. government employee stationed at the consulate there was knocked unconscious by something akin to a strong energy beam".

U.S. Congress passed the Havana Act in 2021 authorising the State Department, CIA and other U.S. government agencies to provide payments to staff and their families who have been affected by the ailment during assignment.

https://www.yahoo.com/news/russian-military-intelligence-unit-may-060223890.html

Will Oral Weight-Loss Drugs Break Open an Already Lucrative Market?

 Sales of Eli Lilly and Novo Nordisk’s injectable GLP-1 drugs have soared in weight-loss indications, with Lilly’s Zepbound overtaking Novo’s Wegovy in new U.S. prescriptions for the first time last month. Obesity is a major global health crisis, and the allure of a market that could exceed $100 billion has companies throwing their R&D dollars into treating it. The next big move for the space—an easy-to-pop pill—is already well underway.  

Along with Novo and Lilly, Pfizer, Roche and a handful of smaller biotechs are racing to create an oral GLP-1 option with efficacy rivaling that of the currently approved injectable drugs. A pill could be the ticket to truly cracking open the massive market, Graig Suvannavejh, a senior biopharmaceuticals and biotechnology equity research analyst at Mizuho Americas told BioSpace in an email. 

“Oral [GLP-1s] hold huge potential in lowering prices and broadening access for patients,” he said, adding that it could potentially bring them to a more global population.

Lilly Leads a Crowded Pipeline

Now in Phase III with its small molecule orforglipron, Lilly is leading the oral GLP-1 race. The company is already ramping up manufacturing capacities as it advances the pill into late-stage development.

In June 2023, the company shared Phase II data that showed weight loss of between 9.4% and 14.7% after 36 weeks on the drug compared to 2.3% for the placebo group. Lilly expects Phase III results in 2025, according to a company spokesperson. The results were comparable to the Zepbound injection, which led to weight loss of up to 15.7% after 72 weeks of treatment in the SURMOUNT-2 trial versus 3.3% for those on placebo.

Not to be left behind, Novo last month touted data from its Phase I trial of amycretin, a next-generation co-agonist of both the GLP-1 and amylin receptors. After 12 weeks, patients taking the drug saw 13.1% weight loss.

In December 2023, Roche bought its way into the obesity game with the $2.7 billion acquisition of Carmot Therapeutics. The deal gave Roche access to the biotech’s two dual agonists targeting GLP-1 and GIP receptors (a similar mechanism to Zepbound), as well as a once-daily oral GLP-1 drug currently in Phase I. At the time, Levi Garraway, the company’s chief medical officer and head of global product development, said the portfolio offered “different routes of administration and opportunities to develop combination therapies.”

Pfizer is working on an oral formulation of its oral GLP-1 receptor agonist of danuglipron. Last year, the pharma company chose to focus on a once-daily formulation and drop the twice-daily version of danuglipron due to smaller weight reductions than the competition and high rates of side effects and patient dropouts, STAT News reported. The pill is currently in a Phase I trial comparing pharmacokinetics between immediate and modified-release formulations.

On the biotech side, Viking Therapeutics is working on both a subcutaneous and oral formulation of its dual GLP-1/GIP receptor agonist. Viking unveiled promising Phase I data in March demonstrating dose-dependent decreases in mean body weight. Participants treated with the highest dose level of the drug saw a 3.3% drop in mean body weight relative to placebo.

Meanwhile, San Francisco–based Structure Therapeutics believes the successful Phase II trial of its oral small molecule GLP-1 asset proves its best-in-class potential. Interim results at eight weeks showed a mean weight drop of 5.5%. The company expects to initiate a Phase IIb obesity study in the second half of 2024, according to the announcement.

“Safe and effective oral small molecule GLP-1 receptor agonists would be a significant advance in that they could expand access for many patients for whom this is not now possible,” Structure CEO Raymond Stevens said in a statement.

Improved Accessibility

Despite their exploding popularity, the current GLP-1 injections face accessibility issues due to cost and limited insurance coverage, challenges oral versions may be able to address to some extent.

Weight loss medications currently aren’t covered by Medicare for obesity, and Medicaid coverage varies by state.

Commercial insurers can cover the drugs if the employer opts in, but many plans require prior authorization, a restriction that wasn’t an issue before GLP-1’s use for weight loss became common, said Michael Glickman, an obesity medicine physician and CEO of Revolution Medicine. An October 2023 survey found that only about a quarter of corporate health insurance plans cover GLP-1 drugs for weight loss, though another 13% were considering adding it as of February 2024.

“The majority of Americans still don’t have access to GLP-1s,” Glickman told BioSpace.

He hopes the approval of oral drugs will alleviate some of the pricing burden, as more medications on the market will drive competition. Suvannavejh concurred, saying he believes the arrival of oral GLP-1 drugs on the market will drive the cost down for consumers and perhaps also lead to better coverage from insurers. 

Glickman also pointed out that a small percentage of the population is needle averse enough to not want to inject themselves. Pfizer believes the factor plays a role why the current obesity injections are underutilized, a representative told BioSpace in an email. The spokesperson added that Pfizer expects a small molecule oral GLP-1 could be “well-reimbursed.”

A Lower Manufacturing Burden

Drug shortages of GLP-1s have been consistently frustrating for patients, Glickman said, adding that his practice receives multiple calls each week from patients having trouble refilling their obesity medications. In January, the World Health Organization issued a warning to patients regarding falsified versions of the drugs as shortages continue to limit GLP-1 drug access.

“It’s very challenging to keep patients on track when you can’t maintain medication consistency,” Glickman said.

Creating and packaging injectable peptides is a complex process. If successful, the arrival of oral formulations to the market should ease the current bottleneck, he added. “The complexity of producing an oral medication is going to be a lot simpler than producing a sterile subcutaneous product.” Additionally, having multiple options on the market would allow patients to pivot from one brand to another in the face of a supply chain issue, Glickman said.

With the current global focus on obesity, large companies with ample production capacity simply have to tap into the opportunity, while small companies are betting on “building a better mousetrap,” or formulation, in order to compete in the crowded space, Suvennevejh said. If these drugs do eventually make it to market, “there’s plenty of room to go around.”

https://www.biospace.com/article/will-oral-weight-loss-drugs-break-open-an-already-lucrative-market-/

FDA Action Alert: Vanda, Basilea and J&J/Legend

 After a hectic month, the FDA’s calendar appears to be easing up a bit. In the next two weeks, the regulator is facing just three major target action dates, including one potential CAR-T therapy approval that could push the class into earlier lines of treatment for multiple myeloma.

Read below for more.

Vanda Seeks Expansion of Fanapt into Bipolar Disorder

Vanda Pharmaceuticals is proposing its atypical antipsychotic Fanapt (iloperidone) as a treatment for bipolar I disorder. The FDA’s verdict is due on April 2.

In January, the Washington, D.C.-based biotech published Phase III data for iloperidone in the Journal of Clinical Psychiatry. The randomized, double-blinded and placebo-controlled study enrolled 414 adults with bipolar mania and demonstrated that iloperidone could induce significant symptom improvement within four weeks of treatment.

For instance, scores on the Young Mania Rating Scale, an 11-point clinical interview scale, were significantly better in the iloperidone group. The antipsychotic treatment likewise led to better scores on the Severity and Change subscores of the Clinical Global Impressions scale.

As for safety, treatment-emergent adverse events were more common in the iloperidone arm, though most were mild or moderate. Eighteen patients in the iloperidone group dropped out due to side effects, as opposed to 11 in the placebo arm. There were no deaths resulting from treatment toxicities.

Iloperidone is an atypical antipsychotic whose exact mechanism of action is still unknown, according to its label. Nevertheless, Vanda proposes that iloperidone exerts its effects by inhibiting the dopamine type 2 and serotonin type 2 pathways.

Iloperidone was approved in 2009 for the treatment of schizophrenia in adults. It comes with a boxed warning for a heightened risk of death in elderly patients suffering from dementia-related psychosis.

Basilea Awaits Approval for Antibiotic

By April 3, the FDA is expected to release its decision on Basilea Pharmaceutica’s New Drug Application (NDA) for its investigational antibiotic ceftobiprole for Staphylococcus aureus bacteremia (SAB), acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP).

Designed to be administered intravenously, ceftobiprole is the active portion of the prodrug ceftobiprole medocaril. The drug candidate is a cephalosporin antibiotic that has shown rapid bacteria-killing properties with proven activity against the Gram-positive S. aureus, including methicillin-resistant strains, according to Basilea. Ceftobiprole has also shown potency against Gram-negative bacteria.

Basilea supported its NDA, which the FDA accepted in October 2023, with three Phase III studies. The first, dubbed ERADICATE, tested ceftobiprole in SAB patients.

Basilea published data from ERADICATE in September 2023, demonstrating that ceftobiprole was non-inferior to daptomycin in terms of the study’s primary endpoint of treatment success, which was a composite of survival, symptom improvement, bacteremia clearance, no new infection-related complications and no need for other antibiotics.

The NDA also included data from the Phase III TARGET study, which focused on ABSSSI, and another late-stage trial in CABP.

J&J, Legend Look to Push Carvykti into Earlier Lines of Multiple Myeloma Treatment

The FDA’s biggest decision in the coming week is for the CAR-T therapy Carvykti (ciltacabtagene autoleucel, cilta-cel), which its manufacturers Johnson & Johnson and Legend Biotech are proposing for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one previous line of therapy.

The regulator’s decision is due on April 5, 2024.

Carvykti works by reprogramming a patient’s own T-cells, inducing the expression of a receptor that allows these immune cells to seek out and destroy cancer cells expressing the BCMA protein. Currently, Carvykti is indicated for patients who have undergone at least four prior lines of therapy, according to its label.

J&J and Legend are seeking an earlier-line approval for Carvykti on the back of their Phase III CARTITUDE-4 trial, which compared the CAR-T treatment to standard chemotherapy regimens, including pomalidomide-bortezomib-dexamethasone and daratumumab-pomalidomide-dexamethasone. The study showed that Carvykti reduced the risk of disease progression or death by 74% versus standard of care.

Earlier this month, the FDA’s Oncologic Drugs Advisory Committee voted 11–0 to back Carvykti’s approval as an earlier-line therapy. The unanimous support came despite what the FDA’s internal reviewers flagged as a “higher rate of early deaths” in patients treated with Carvykti.

The FDA has been erring on the side of caution when it comes to CAR-T therapies. In November 2023, the regulator launched a probe into the drug class, particularly regarding reports of secondary T-cell malignancies in treated patients. In January 2024, the FDA called for a class-wide boxed warning to alert prescribers and patients to such risks.

https://www.biospace.com/article/fda-action-alert-vanda-basilea-and-j-and-j-legend/