Apellis Dives on Worse-Than-Expected Syfovre Sales

 Apellis stock plunged Tuesday after third-quarter sales of the company's eye drug, Syfovre, widely missed Wall Street's expectations.

During the September quarter, Syfovre generated $152 million in sales. But analysts called for $163 million to $167 million in sales, according to various reports. Sales fell 1.7% sequentially. This was Syfovre's first sequential decline since launching last year.

Apellis Pharmaceuticals (APLS) delivered more than 84,500 commercial vials of Syfovre, which treats geographic atrophy, plus 4,000 samples. On a quarter-over-quarter basis, that's up 7%. Apellis blamed a higher gross-to-net adjustment during the quarter for the revenue miss.

"While many were expecting a miss on Syfovre revenue, this is worse than we believe they were expecting, and though obviously a disappointment, we see the volume growth as a bright spot indicating continued demand for Syfovre," William Blair analyst Lachlan Hanbury-Brown said in a report to clients.

https://www.investors.com/news/technology/apellis-stock-apellis-pharmaceuticals-earnings-q3-2024/

Bioventus nudges guidance up after Q3

 2024 Financial Guidance:

For the twelve months ending December 31, 2024, the Company now expects:

• Net sales of $562 million to $567 million, reflecting an increase of $2.5 million from the midpoint of previous guidance
• Adjusted EBITDA* of $104 million to $107 million
• Non-GAAP EPS* of $0.40 to $0.42, reflecting an increase of $0.02 from the midpoint of previous guidance

Recent Business Highlights

Bioventus continues to advance its strategic priorities with key achievements, including the following:

• Delivered four consecutive quarters of double-digit revenue growth in Pain Treatments and Surgical Solutions, which contributed to an 8.4% increase in Adjusted EBITDA*
• Reached an agreement to divest the Company's Advanced Rehabilitation Business for up to $45.0 million, which is anticipated to close near the end of 2024 or early 2025 and is expected to reduce debt and enable greater focus on execution within our remaining core businesses

Third Quarter 2024 Earnings Conference Call:

Management will host a conference call to discuss the Company’s financial results and provide a business update, with a question and answer session, at 8:30 a.m. Eastern Time on November 5, 2024. Those who would like to participate may dial 1-833-636-0497 (domestic and international) and refer to Bioventus Inc.

A live webcast of the call and any accompanying materials will also be provided on the investor relations section of the Company's website at https://ir.bioventus.com/.

The webcast will be archived on the Company’s website at https://ir.bioventus.com/ and available for replay until November 4, 2025.

https://www.globenewswire.com/news-release/2024/11/05/2974835/0/en/Bioventus-Reports-Third-Quarter-Financial-Results.html

'FBI warns against two fake videos as officials combat election disinformation'

 The FBI on Tuesday warned Americans about two new fake videos falsely citing terror threats and voter fraud, the latest in a string of disinformation that officials expect will intensify as voters head to the polls on Election Day and in the weeks afterward.

One fabricated video purporting to be from the federal law enforcement agency falsely cited a high terror threat and urged Americans to "vote remotely," while another video includes a fake press release alleging to be from the agency and alleging rigged voting among inmates in five prisons.

Both are "not authentic," the Federal Bureau of Investigation said in a statement, "Attempts to deceive the public with false content about FBI threat assessments and activities aim to undermine our democratic process and erode trust in the electoral system." 

Federal, state and local officials have been warning Americans about attempts to undermine the election with wrong information and have urged U.S. voters to seek out credible information from reliable sources.

U.S. intelligence agencies have also said this year's contest faces an unprecedented disinformation campaign from foreign adversaries and that Russia and others aim to fan divisive narratives amid the election, an accusation Russia has denied.

On Monday, U.S. intelligence agencies said they expect overseas influence operations to "intensify through election day and in the coming weeks," particularly in the seven key battleground states of Arizona, Georgia, Michigan, Nevada, North Carolina, Pennsylvania and Wisconsin.

Still, U.S. cybersecurity agency director Jen Easterly has said her department has not seen evidence of any activity that could directly impact the outcome of Tuesday's election, despite the surge in disinformation.

U.S. intelligence agencies last week blamed Russia for a false video purporting to show a Haitian immigrant claiming to have voted multiple times in the U.S. state of Georgia. Over the weekend, the FBI warned about several other fake videos.

https://www.marketscreener.com/news/latest/FBI-warns-against-two-fake-videos-as-officials-combat-election-disinformation-48262748/

AstraZeneca Bolsters Obesity Pipeline With Promising Early Data for Candidates

 

While expected and seen as largely incremental, Jefferies analyst Peter Welford in a Tuesday note to investors said the detailed data for three early-stage assets support moving them into Phase IIb studies and creates a “foothold” for AstraZeneca in the weight loss space.

AstraZeneca on Monday touted the competitive potential of its weight management pipeline at The Obesity Society’s ObesityWeek 2024 meeting in San Antonio, Texas, revealing early data for its oral GLP-1, a selective amylin agonist and a fixed-dose combination therapy.

Leading the pharma’s weight loss program is AZD5004, a small molecule oral GLP-1 receptor blocker licensed in November 2023 from Shanghai-based biotech Eccogene. At ObesityWeek, AstraZeneca unveiled early data for AZD5004, touting a clean safety profile for the investigational pill.

AZD5004 in healthy participants did not result in serious adverse events, while gastrointestinal toxicities became increasingly common at doses at or above 50 mg. In type 2 diabetes patients on metformin treatment, AZD5004 led to more side effects than placebo, particularly gastrointestinal in nature—though none of the side effects were serious.

The GLP-1 resulted in 5.8% weight loss after four weeks of treatment in type 2 diabetes patients. Pharmacodynamic data showed that all tested doses of AZD5004 lowered fasting plasma glucose during a mixed meal tolerance test.

Jefferies analyst Peter Welford said the initial AZD5004 data “showcase tolerability” with “encouraging” pharmacokinetics.

BMO Capital Markets analyst Etzer Darout in a note to investors said that AstraZeneca believes that AZD5004 is “differentiated” from other GLP-1 therapies in development and on the market, particularly given its “favorable tolerability.” Further helping AZD5004 distinguish itself in the crowded obesity space is its “reduction in glucose and body weight” in patients with type 2 diabetes and its “simplified manufacturing path,” Darout wrote.

Also at ObesityWeek, AstraZeneca presented early data for AZD6234, its long-acting amylin receptor agonist which, unlike most obesity therapies, targets the amylin pathway but is designed to achieve broadly similar effects—delay gastric emptying, suppress appetite and promote the release of glucagon from the pancreas.

The Phase I study demonstrated that AZD6234 was well-tolerated by healthy participants, with no deaths or serious adverse events recorded. However, pooled global data showed that side effects were more common in AZD6234-treated patients versus placebo, with mostly episodes of nausea, vomiting and decreased appetite.

In terms of efficacy, the early study showed that patients treated with subcutaneous AZD6234 experienced a “statistically significant decrease in body weight” compared with placebo.

AstraZeneca is positioning AZD6234 as an effective treatment alternative for patients who are intolerant to incretin therapies, according to Darout, who noted that preclinical data indicate that the amylin asset could promote fat-selective weight loss. Other GLP-1 therapies have resulted in the loss of lean muscle mass.

Darout commented that the AZD6234 ObesityWeek data were limited with “little to build enthusiasm as expected.” Still, he said AstraZeneca is developing AZD6234 and AZD9550 as a potential fixed-dose combination therapy for patients with obesity. The amylin and GLP-1/glucagon combo, which “aims to improve weight loss and organ protection,” is a potential once-weekly therapy with Phase IIb trial planning underway.

“We like AZN’s optionality for these programs as well as potential combinations with other assets in the portfolio,” Darout said. However, he added that until “further de-risking” of the pharma’s obesity portfolio—through strong efficacy and clean safety data in larger studies—his firm will continue to adopt a more “conservative” revenue estimate of $865 million by 2032, a far cry from AstraZeneca’s $5 billion peak projection for its metabolic business.

“We’re more conservative given the earlier stage of development of these assets and look to further de-risking from upcoming Phase II datasets,” Darout said.

At ObesityWeek on Sunday, Viking Therapeutics unveiled early data from the first-in-human study of its investigational oral obesity drug VK2735, touting strong weight loss in healthy adults and an encouraging safety profile.

https://www.biospace.com/drug-development/astrazeneca-bolsters-obesity-pipeline-with-promising-early-data-for-candidates

FDA Delays Decision on Merus Bispecific Antibody to Review CMC Info

 

Despite the PDUFA date being extended by three months for Merus’ zenocutuzumab, Truist Securities analyst Asthika Goonewardene in a Tuesday note to investors said the delay is not a cause for concern with an approval expected.

Merus on Tuesday announced that the FDA has extended its review of the investigational bispecific antibody zenocutuzumab, which the biotech is proposing as a treatment for non-small cell lung cancer and pancreatic ductal adenocarcinoma patients carrying certain genetic mutations.

The delay will give the regulator “sufficient time” to review additional Chemistry, Manufacturing and Controls (CMC) information that the company submitted in response to a previous request. Merus emphasized that the FDA did not request additional clinical efficacy or safety data, nor did the agency point out problems with zenocutuzumab’ data package.

The new target action date is Feb. 4, 2025. The previous PDUFA date was Nov. 4, 2024.

Zenocutuzumab is a bispecific antibody that works by binding to the HER2 protein and disrupting the binding between the HER3 receptor and neuregulin or its associated fusion. Preclinical studies have helped establish that this mechanism of action prevents the proliferation and survival of cancer cells.

Merus is developing zenocutuzumab for non-small cell lung cancer and pancreatic ductal adenocarcinoma positive for fusions of the NRG1 gene. While these genetic anomalies are rare, they are often associated with oncogenic events in various cancers. The FDA accepted Merus’ Biologics License Application on May 6, 2024, and gave it Priority Review.

In a note to investors, Truist Securities analyst Asthika Goonewardene said that a third-party manufacturer is handling the manufacturing of zenocutuzumab and “our read is that the FDA questions were something that the third-party should have anticipated and addressed earlier,” adding that his firm does not think there is a serious underlying issue.

Leerink Partners analyst Andrew Berens said that the delay “may pressure” Merus’ stock, though his firm does not expect it to be of significant consequence to Merus since “zeno is not core to most investor’s theses.”

“We do not see readthrough to [petosemtamab] and the rest of the pipeline as this is limited to a manufacturing issue,” Berens wrote.

BMO Capital Markets analyst Etzer Darout largely agreed, calling zenocutuzumab a “modest commercial opportunity” for Merus, with estimated peak sales of $462 million globally. The biotech “has expressed interest in partnering the program,” suggesting that Merus would rather invest its capital into the more promising petosemtamab, Darout said. The delay “does not impact our MRUS thesis,” he added.

Petosemtamab is a human, full-length IgG1 monoclonal antibody designed to bind to EGFR and LGR5, both of which are known cancer targets. According to Merus’ website, petosemtamab has three independent mechanisms of action—it blocks EGFR signaling, prevents the LGR-5-dependent internalization and degradation of EGFR in cancer cells and boosts the body’s anti-cancer response.

Merus is developing petosemtamab for the first-line treatment of head and neck squamous cell carcinoma, with a Phase III trial initiated in the third quarter of 2024. In May, the biotech reported Phase I/II data for the antibody, touting a 67% overall response rate in patients regardless of PD-L1 expression levels.

Petosemtamab is also being assessed as a second-line treatment for metastatic colorectal cancer, with a Phase II study initiated in the third quarter.

https://www.biospace.com/fda/fda-delays-decision-on-merus-bispecific-antibody-to-review-cmc-information

Alkermes upped to Buy from Hold by Stifel

 Target to $36 from $25

https://finviz.com/quote.ashx?t=ALKS&p=d

ZyVersa: Protecting Pancreatic Islet Beta Cells, Curbing Progress from Obesity to Insulin Resistance, T2D

 

• During obesity, inflammasome-driven inflammation results in significant loss of pancreatic islet beta cell mass, severely impairing the insulin secreting capacity of the remaining beta cells.
• Preserving pancreatic islet beta cell function is key to prevention of insulin resistance and development of type 2 diabetes.
• The published data showed that inflammasome NLRP3 inhibition was protective of pancreatic islet beta cells, restoring their function and improving metabolic status in an obesity DIO mouse model.
• Data from this article support ZyVersa’s development of Inflammasome ASC Inhibitor IC 100 for obesity and its associated comorbidities to be used as an add-on to incretin therapy.

https://www.globenewswire.com/news-release/2024/11/05/2974772/0/en/ZyVersa-Therapeutics-Highlights-Published-Data-Demonstrating-the-Potential-of-Inflammasome-Inhibition-to-Protect-Pancreatic-Islet-Beta-Cells-and-Attenuate-Progression-from-Obesity-.html