At its annual Vaccines Day and Business Update on Wednesday, Moderna (MRNA) sought to show analysts and investors just how much its pipeline has advanced, four years after making history by harnessing mRNA technology and competing head-on with Pfizer and BioNTech to produce one of two COVID-19 vaccines that reached the market and addressed the pandemic.

Moderna had plenty to announce starting with COVID-19, where the company trumpeted its next-gen, refrigerator-stable vaccine for the virus (mRNA-1283) as its fourth respiratory vaccine to successfully meet Phase III endpoints.

Two more Phase III readouts are planned this year: One is for a combination influenza/COVID-19 vaccine candidate (mRNA-1083), now in the 8,075-participant P301 trial (NCT06097273). The other Phase III readout is for a vaccine candidate designed to protect from cytomegalovirus (CMV; mRNA-1647), now under study in the CMVictory trial (NCT05085366) in ~7,300 women ages 16–40. CMVictory has documented 50 infections to date, with 81 cases needed to trigger an interim analysis from the trial’s Data Safety Monitoring Board.

Another three vaccine candidates—designed to protect from Epstein-Barr virus, Varicella-Zoster virus, and norovirus—are advancing toward Phase III after reporting positive data from clinical trials. Those and other candidates across Moderna’s pipeline of 28 vaccines addressing respiratory, latent and other pathogens together account for a cumulative $52 billion total addressable market—$27 billion for the respiratory programs, the remaining $25 billion for the latent viral programs.

Arguably, however, Moderna’s best news had less to do with clinical data or regulatory decisions than it did with capital.

In an announcement timed to Moderna’s Vaccines Day event, Blackstone Life Sciences committed up to $750 million to fund Moderna’s influenza program. That’s no small commitment for Blackstone, since it represents up to 9% of Blackstone’s more than $8 billion in assets under management.

If the flu program develops successful vaccines, Blackstone will be eligible for milestone payments and royalties. Moderna—which will retain full rights and control of the influenza program—agreed to recognize the Blackstone funding as a reduction in its research and development (R&D) expenses. However, Moderna did not change its 2024 guidance to investors, which calls for the company to spend $4.5 billion on R&D.

Moderna’s vaccine updates appeared only mildly interesting to investors, as shares rose 3% Wednesday from $107.41 to $110.59. But the momentum didn’t last as shares more than gave up that gain, sliding 4% on Thursday to $106.56 (markets were closed for Good Friday).

Over the past six months, however, Moderna investors have fared better. The company’s shares soared 53% between November 9, when the stock closed at $69.51, and January 8, when they reached a year-to-date high closing price of $115.44. That day Moderna offered several positive announcements at the 42nd Annual J.P. Morgan Healthcare Conference, including projections of $4 billion in product sales this year, a return to sales growth in 2025, and a break-even 2026.

Mixed assessment from analysts

Analysts have been decidedly mixed in their assessment of Moderna. On the bullish side, Jefferies analyst Michael Yee raised his firm’s 12-month price target on Moderna shares 16%, from $115 to $125. He retained Jefferies’ “Buy” rating on the stock.

On the bearish side, Mani Foroohar, MD, senior managing director, Genetic Medicines and a senior research analyst at Leerink Partners, lowered his firm’s Moderna price target 3%, from $61 to $59. Foroohar also reiterates Leerink’s “Underperform” rating for Moderna shares.

Foroohar dismissed the portfolio updates and AI dose selection tool as “scientifically interesting, but unlikely to compensate for core business erosion in the near/medium term, in our view.”

“While few transaction details were disclosed, gross margin contraction from royalty/ milestone payments without offsetting improvement in R&D guidance are incrementally negative for MRNA’s ability to reach cash flow breakeven by 2026.”

Two other analysts kept their ratings and price target projections in place: Needham’s Joseph Stringer reiterated his firm’s “Hold” rating, while RBC Capital’s Lucas Issi kept his firm’s “Outperform” rating and price target, now at $125.

Bill Maughan, PhD, equity research senior analyst-biotechnology with Canaccord Genuity, also retained his firm’s “Hold” rating on Moderna shares, as well as the firm’s price target of $91.

“We acknowledge the company’s strengths in manufacturing, R&D, and clinical development,” Bill Maughan, PhD, equity research senior analyst-biotechnology with Canaccord Genuity, began in a research note, before adding: “We continue to view the late-stage infectious disease vaccine portfolio as a relatively high probability, low commercial reward opportunity.”

Maughan took a more positive view of the $750 million Blackstone financing.

“We welcome this type of deal, as our view of a mismatch between R&D expense and commercial opportunity is what is holding us back from being more constructive on [Moderna],” he wrote.

Flu program insight

Vaccines Day offered some insight into the flu program that Blackstone has agreed to fund going forward. Moderna said it is on track to file for approvals this year for its lead flu candidate, the seasonal flu vaccine mRNA-1010, which has shown positive safety and efficacy results across three Phase III trials.

In the most recent Phase III trial, P303 (NCT05827978), mRNA-1010 showed higher HAI geometric mean titers and seroconversion rates for all four flu strains studied (A/H1N1, A/H3N2, influenza B/Yamagata, B/Victoria), compared with GlaxoSmithKline (GSK)’s Fluarix Quadrivalent.

With those results, Moderna bounced back from a setback in April 2023, when the company acknowledged that an earlier version of the vaccine did not meet the statistical threshold necessary to declare early “noninferiority” success in an interim efficacy analysis for its Phase III P302 trial (NCT05566639), because it had too few cases.

Moderna would have needed to enroll patients for a second season to accrue the needed cases—something the company opted not to do after its updated formulation of mRNA-1010 succeeded in the P303 trial.

mRNA-1010 remains under study in a fully enrolled older adult extension study of P303, where the vaccine candidate is being studied against Sanofi’s Fluzone® High-Dose Quadrivalent.

mRNA-1010 leads a portfolio that includes four additional flu vaccines in Phase II development (mRNA-1020, -1030, -1011, and -1012); three combination vaccines, flu/COVID in Phase III (mRNA-1083), flu/COVID/RSV (mRNA-1230), and flu/RSV (mRNA-1045), the latter two in Phase II; and a Phase I pandemic flu vaccine (mRNA-1018).

The only other flu candidate for which Moderna offered a full update on Wednesday was the flu/COVID vaccine mRNA-1083: A Phase III trial in adults aged 50 years and older is fully enrolled, with data expected later this year.

Last October, Moderna reported that mRNA-1083 generated positive interim results in a Phase I/II trial (NCT05827926) by achieving hemagglutination inhibition antibody titers similar to or greater than Fluarix and Fluzone, and achieving SARS-CoV-2 neutralizing antibody titers similar to the company’s Spikevax bivalent booster.

Moderna did touch on mRNA-1230, by hinting it may co-administer the triple flu/COVID/RSV combo as two separate doses, one of mRNA-1083 and the other of its RSV vaccine (mRNA-1345), depending on Phase III data.

May 12 PDUFA date

mRNA-1345 is under FDA review, with the agency setting a Prescription Drug User Fee Act (PDUFA) target decision date of May 12. “If the outcome is positive, we anticipate that ACIP will include mRNA-1345 on the agenda in late June,” Moderna CEO Stéphane Bancel told analysts February 22 on the company’s quarterly earnings call.

ACIP is the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP).

If approved, mRNA-1345 would be indicated for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease (ARD) in adults ages 60 years or older.

“RSV is the key launch in 2024,” Yee of Jefferies declared Wednesday in a research note.

Yee also noted that while market watchers are debating how successful the vaccine will be, Moderna has two points in its favor. One is reported strong direct lines to major pharmacy heads, which should help drive contracting activity. The other is Moderna’s pre-filled syringe for administering the vaccine, which leads to delivery of four times the vaccines in one hour that GlaxoSmithKline (GSK) and Pfizer can deliver with their RSV treatments (Arexvy and Abrysvo™, respectively), which require additional steps for reconstituting.

Moderna has another potential winner in its next-gen COVID-19 vaccine mRNA-1283, which aced the NextCOVE (NCT05815498) pivotal trial by eliciting a higher immune response against both the Omicron BA.4/BA.5 and original virus strains of SARS-CoV-2, compared to the company’s marketed Spikevax® COVID-19 vaccine (mRNA-1273.222). That result was most acutely seen in participants over age 65, a population at highest risk for severe outcomes.

“This success has read-through not only to approval from regulators but also to the company’s flu/COVID-19 combination vaccine mRNA-1083 and could provide supply chain benefits by increasing refrigeration shelf-life of pre-filled syringes, which are easier to use at points of care,” William Blair analysts Myles R. Minter, PhD, and Sarah Schram, PhD, wrote today in a research note, before cautioning: “Successful advancements in its COVID-19 program look promising but may ultimately be capped by commercial and perception factors that have generated historically poor vaccination rates in the U.S.”

Also expressing caution was Foroohar, in a research note Thusday: “While the trial met non-inferiority primary endpoints, as expected, whether mRNA-1283 changes the commercial outlook for MRNA’s COVID franchise is unclear.”

Sales of COVID-19 drugs and vaccines have shriveled as the pandemic evolved into an endemic. Moderna’s Spikevax vaccine sales skidded 64% last year, to $6.671 billion from $18.435 billion, and the company has projected only ~$4 billion in net sales for this year.

However, Moderna surprised market watchers last year by finishing 2023 with $8.362 billion in net income on $19.263 billion in total revenue, including grant and collaboration revenue. That sent Moderna shares rising 13.5%, from $87.59 to $99.44. when 2023 results were announced on February 22.

Leaders & laggards

  • Gamida Cell (GMDA) shares cratered 88% from 34 cents on Tuesday to 4 cents on Thursday, after the company said Wednesday it entered into a restructuring with funds managed by its principal lender Highbridge Capital Management. Gamida Cell said it expected the agreement to provide it with a long-term financial runway and support commercialization of its Omisirge® (omidubicel-onlv) cell therapy for blood cancers. Highbridge agreed to convert $75 million of its existing unsecured convertible senior note into equity in Gamida Cell, which will receive $30 million of new capital from Highbridge. Gamida Cell will go private, wholly owned by Highbridge. The reorganized company will issue contingent value rights of up to $27.5 million Gamida Cell shareholders, tied to achieving revenue and regulatory milestones.
  • iBio (IBIO) shares nearly tripled, zooming 192% from $1.15 to $3.36 on Wednesday, after the company agreed to partner with privately held AstralBio to discover, engineer, and develop novel antibodies to treat obesity and other cardiometabolic conditions, to be funded by part of the net proceeds from a $15 million private placement. iBio has granted AstralBio an exclusive license to its AI technology to identify and engineer four cardiometabolic disease targets, for which AstralBio may continue preclinical development toward an IND application. iBio has an exclusive option to license three cardiometabolic targets from AstralBio and will, upon exercise, gain rights to develop, manufacture, and commercialize them. The companies also agreed to launch a novel lead program targeting the transforming growth factor beta (TGFb) superfamily to treat muscle wasting and obesity.
  • Nuvation Bio (NUVN) shares dipped 3% from $2.31 to $2.25 on March 25 before leaping 76% over the following two days, to $3.97 on Wednesday, after the company said it agreed to acquire AnHeart Therapeutics, in an all-stock transaction of undisclosed value. The deal would transform Nuvation into a late-stage global oncology company with pipeline programs that include taletrectinib, a Phase II next-generation ROS1 inhibitor designed to treat ROS1-positive non-small cell lung cancer, completing two pivotal studies; and safusidenib, a mutant IDH1 inhibitor now in a global Phase II study of patients with grades 2 and 3 IDH1-mutant glioma. Upon closing of the acquisition, expected in the second quarter, AnHeart’s former shareholders will own approximately 33% of Nuvation Bio, whose current shareholders will own the remainder.
  • Xilio Therapeutics (XLO) shares rocketed 69% on Thursday, from 64 cents to $1.08, then climbed another 20% to $1.30 after hours, after the company joined Gilead Sciences (GILD) to announce an exclusive licensing agreement to develop and commercialize Xilio’s Phase I tumor-activated IL-12 program, XTX301. Gilead agreed in return to pay Xilio $30 million cash upfront, invest $13.5 million in XIlio stock, and pay Xilio up to $604 million, including additional equity investments, a transition fee, and payments tied to achieving development, regulatory, and sales-based milestones, plus tiered royalties ranging from high single digits to mid-teens on annual global net product sales. Gilead shares inched up 0.3%, from $73.01 to $73.25.
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