Candel Pairs HSV Vectors with Carl June's CAR-T Cells in Solid Tumor Pact

 Candel Therapeutics revealed a collaboration with the University of Pennsylvania Wednesday to assess the combination of Candel’s herpes simplex virus (HSV) vectors and UPenn’s CAR-T cell treatments in solid tumor models.

The alliance will involve cutting-edge cell immunotherapy work done in Penn’s T Cell Engineering Lab, under Carl June’s Center for Cellular Immunotherapies.

Neil Sheppard will be in charge of Penn’s contribution to the partnership. Sheppard heads the T Cell Engineering Lab under the June lab, using genetic engineering to boost the function of CAR-T cells, natural killer cells and other immune cells for use against diseases. 

Meanwhile, Candel will contribute its proprietary enLIGHTEN platform, which produces genetically engineered HSV vectors that deliver a gene payload, leading to tumor cell death or strengthening the body’s innate and adaptive anti-cancer immune response.

Candel injects its vectors directly into the tumor or surrounding tissue to avoid systemic side effects.

Under the terms of the agreement, the two parties will jointly investigate the use of these novel engineered viruses to break down barriers to CAR-T treatments and assess the impacts of this combo on solid tumors.

Penn and Candel will keep full rights over their existing respective intellectual properties. 

The collaborators will also have the right to take any promising combination from the partnership to clinical trials.

CAN-3110, an HSV-based therapeutic engineered such that a crucial viral replication gene is put under the control of a tumor-specific promoter, is Candel's lead product candidate.

These modifications allow CAN-3110 to replicate actively and specifically inside tumor cells despite an overall suppressive environment. In animal models, this action results in strong anti-cancer cytolytic activity.

In a statement, Sheppard explained that cancer’s microenvironment is a critical stumbling block for many cell-based cancer therapies. This is due to an overall suppressive milieu that contains elements that impede T-cell movement and function and dampens T-cell expansion, he said. 

Paul Peter Tak, M.D., Ph.D., president and chief executive officer of Candel, noted that the alliance would specifically look into the tumor microenvironment and determine if the company’s viral immunotherapies could enable Penn’s cell therapies.

For more than 20 years, the June lab has focused on improving and developing new forms of T cell-based therapies and has since discovered many crucial and foundational principles for the technology. The lab was also the first to perform human studies of CAR-T cell technology.

https://www.biospace.com/article/carl-june-s-upenn-lab-teams-up-with-candel-to-combine-viral-immunotherapy-with-car-t/

DiaMedica Ischemic Stroke Program Remains on Hold with Plans for Additional Studies

 Minneapolis-based DiaMedica Therapeutics plans to conduct additional studies in order to resolve a clinical hold on its DM199 program for the treatment of acute ischemic stroke (AIS), the company announced Wednesday.

The FDA placed the hold on the Phase II/III ReMEDy 2 trial in July due to three serious adverse events of acute hypotension during IV infusion of the drug.

Rick Pauls, DiaMedica’s president and CEO, stated in a conference call that the additional data will be drawn from in vitro data and in-use data.

"Although the timeline isn’t solid, it should take approximately two months. We’ve also put in place mitigation protocols to prevent hypotension," he said. 

DM199 is a recombinant form of human tissue kallikrein-1 (KLK1). KLK1 deficiency leads to the disruption of a range of physiological processes and is believed to play a role in strokes, chronic kidney disease, retinopathy, vascular dementia and resistant hypertension. It received Fast Track designation from the FDA in September 2021 to treat AIS.

DM199 is known to cause low blood pressure (hypotension). Data to date found that the type of intravenous (IV) bags used in the ReMEDy 1 trial, where there were no hypotensive events, were different than those used in the ReMEDy 2 trial, where the events occurred.

The analysis found there were significant differences in protein binding, or sticking, between the two types of IV bags, which affected the amount of drug that was administered.

“The drug can attach to plastics and sticks to the IV bag. The in-use study will determine if any other materials affect the dosing," said Kirsten Gruis, M.D., CMO of DiaMedica during the conference call. 

What Comes Next

In meetings with the FDA, DiaMedica agreed on proposed protocol changes. Gruis noted the company would use a “50% dose reduction” and “start with additional lower infusion rates along with ongoing monitoring of blood pressure.”

If blood pressure drops, the infusion would be halted until it returns to normal, which it typically does within a few minutes.

“The FDA acknowledged these changes and did not recommend others. The severe hypotension cases only occurred in the intravenous subcutaneous study and were quickly mitigated and transient,” Gruis said.

DiaMedica expects a Type A meeting with the FDA, hopefully in the next month. Pauls said the study will be "relatively short." 

Gruis also said that in terms of monitoring for hypotension events, the “patients are in a hospital bed and are already being monitored.”

DiaMedica’s financials remain on track, largely because there were significantly fewer expenses while the trial was halted.

“We began scaling back spending with our CROs, with the net results for the third quarter of $2.3 million in spending,” down from the previous quarter, and it will “remain at approximately these levels until we continue the study," said Scott Kellen, DiaMedica’s CFO. 

“This is a matter of checking all the boxes," Pauls said. "But we believe the drug’s benefit-risk profile will be compelling."

https://www.biospace.com/article/diamedica-makes-plan-with-fda-guidance-to-lift-hold-on-acute-ischemic-stroke-program/

Alnylam Opts Against Phase III Trial for Vutrisiran in Stargardt Disease

 Alnylam Pharmaceuticals released its report for Q3, and tucked between positive financial and drug development updates, the company stated it will no longer be initiating a Phase III trial for Vutrisiran in Stargardt disease.

The trial was set to begin at the end of the year. Alnylam did not give a specific reason for the decision, stating only that it will not initiate the trial as it “continues to evaluate the impact of the Inflation Reduction Act.”

Passed in August, the Inflation Reduction Act has been criticized by many in the biopharma industry. As BioSpace previously reported, Merck CEO Robert Davis said the legislation on pricing would be “highly chilling on future innovation,” and Pharmaceutical Research and Manufacturers of America (PhRMA) CEO Stephen Ubl called the bill’s passage a “tragic loss for patients.”

Some of the provisions of the Inflation Reduction Act include:

• An annual cap of $2,000 on out-of-pocket spending

• Maximum “fair prices” for selected drugs covered under Medicare

• A requirement for the federal government to negotiate prices for some drugs covered under Medicare Part B and Part D 

• A requirement that drug companies pay rebates to Medicare if prices rise faster than inflation 

• Expanding eligibility for full benefits under the Medicare Part D Low-Income Subsidy Program

It is unclear how exactly the Act will affect Alnylam specifically, but vutrisiran has no generic options or biosimilars and is therefore more likely to be affected by the price caps and negotiations. 

In September, the EMA approved vutrisiran as AMVUTTRA for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adults with stage 1 or stage 2 polyneuropathy in Europe and the UK. It was also approved to treat transthyretin (TTR) type familial amyloidosis with polyneuropathy in Japan.

Alnylam has not released data from the Stargardt program that is now being halted, though data from other trials studying the drug have produced positive results.

In Thursday's press release, Alnylam stated it is “considering options for the best path toward advancing an RNAi therapeutic for the treatment of Stargardt disease.”

Stargardt disease is a rare hereditary illness presenting clinically as toxic levels of vitamin A accumulating in the patient’s retina and leading to blindness. There is currently no treatment available for the disease, although there has been some movement in the space. 

In May, the FDA granted Fast Track Designation to Belite Bio’s Stargardt therapeutic designed to slow disease progression and vision loss. Nanoscope Therapeutics and Alkeus are also developing therapeutics for the disease, with both companies currently conducting Phase II trials. 

As for the rest of its pipeline, Yvonne Greenstreet, CEO of Alnylam, said it is on track to reach its five-year goals, dubbed Alnylam P⁵x25.

“The rest of our pipeline continues to progress well...We are encouraged by our steady and continuous execution on all fronts, and believe we are on track to achieve our Alnylam P⁵x25 goals and become a top-tier biotech company," Greenstreet said. 

https://www.biospace.com/article/alnylam-decides-against-phase-iii-trial-for-stargardt-disease-candidate/

Roche's Vabysmo Matches Regeneron's Eylea in Macular Edema

 Two Phase III trials of Genentech (Roche)'s Vabysmo hit the primary endpoint in macular edema caused by branch and central retinal vein occlusion (BRVO), showing non-inferiority to Regeneron's Eylea. 

The data provides yet more ammunition for Vabysmo to compete with Regeneron's Eylea (aflibercept) in the ophthalmology marketplace.

Topline data from the BALATON and COMINO trials, announced Thursday, demonstrated that patients with macular edema from BRVO and central RVO (CRVO) who received Vabysmo injections every four weeks for up to 24 weeks had non-inferior visual acuity gains. This is compared to people receiving Eylea injections every four weeks.

"These encouraging data demonstrate that Vabysmo could potentially provide a new treatment option for people living with retinal vein occlusion," stated Levi Garraway, M.D., Ph.D., CMO and head of global product development for Genentech.

The company indicated it plans to submit the data to regulators. 

Vabysmo is approved in more than 40 countries, including the United States and Europe, for wet (neovascular), age-related macular degeneration (AMD) and diabetic macular edema (DME). The drug targets and inhibits Ang-2 as well as vascular endothelial growth factor-A (VEGF-A).

Vabysmo was launched in the U.S. in January and brought in $292 million by the end of September. It appears to have picked up much of those sales from patients receiving Regeneron's Eylea.

Regeneron won't release third-quarter financials until Nov. 3, but Eylea raked in $1.6 billion in the U.S. in the second quarter.

Evaluate Pharma has projected Vabysmo sales to hit $3.6 billion by 2027, although Evaluate also projected Eylea sales for that period to hit $5.2 billion. However, Eylea will face biosimilar competition starting in 2024.

RVO is the second most common cause of loss of vision from retinal vascular diseases, affecting more than 1 million people in the U.S. In RVO, angiopoietin-2 (Ang-2) levels are increased, which is believed to drive disease progression. 

The disorder causes sudden, painless loss of vision in the affected eye because blockage of the vein restricts normal blood flow in the retina. This results in ischemia, bleeding, fluid leakage and retina swelling, also called macular edema.

In addition to the BALATON and COMINO studies, Genentech is evaluating Vabysmo in AVONELE-X, an extension trial of TENAYA and LUCERNE, studying the long-term safety and tolerability of the drug in wet, or neovascular, macular degeneration.  

Genentech is also conducting RHONE-X, an extension study of YOSEMITE and RHINE, assessing the drug's long-term safety and tolerability in diabetic macular edema. It also launched the Phase IV Elevatum trial in underrepresented patient populations with DME.

Genentech also supports several independent trials of the drug in retinal diseases with a high unmet need.

https://www.biospace.com/article/genentech-s-vabysmo-hits-mark-in-2-macular-edema-studies/

Takeda Posts Lower 1H Profit, Lifts FY22 Outlook

 

• Takeda Pharmaceutical Co Ltd's 
  TAK+1.00%+ Free Alerts
   first-half net profit declined 9.2% from the prior year to ¥166.8 billion. Earnings per share fell 8.1% to ¥108.
• Core net profit grew 9.2% Y/Y to ¥446.7 billion, and core earnings per share were up 34.6% to ¥288.
• Revenue increased by 10.1% to ¥1.97 trillion. Core revenues climbed 19%, and core revenues at constant exchange rates grew 5.5%.
• "Our first half results are driven by strong momentum from our Growth and Launch Products, which grew at 19% year-on-year at a constant exchange rate," said CFO Costa Saroukos.
• The company upgraded the peak sales estimate for its biggest-selling product, Entyvio, based on the potential for further biologic market growth and share expansion and our updated assumption for biosimilar entry timing.
• "We look forward to building on our first half business momentum throughout FY2022."
• Guidance: For FY22, Takeda raised its sales outlook to ¥3,930 billion from the previous guidance of ¥3,690 billion. 
• The company now expects a net profit of ¥307 billion or ¥198 per share, compared to the previously expected ¥292 billion or ¥188 per share, with core EPS of ¥525, up from the previously expected ¥484.
• The company now projects an operating profit of ¥530 billion, up from ¥520 billion expected earlier.

https://www.benzinga.com/general/biotech/22/10/29433936/takeda-posts-lower-1h-profit-lifts-fy22-outlook