Robert Ang, Vor Biopharma CEO

Putting a twist on tar­get­ed ther­a­py, Vor Bio­phar­ma her­alds proof of con­cept for its gene-edit­ed stem cells

Nor­mal­ly in a first-in-hu­man clin­i­cal tri­al, re­searchers are look­ing to find the right dose of their ex­per­i­men­tal drug. Vor Bio­phar­ma set out to do some­thing dif­fer­ent: Not on­ly did it want to see if its ther­a­py, a gene-edit­ed stem cell trans­plant, can en­graft safe­ly; it al­so hopes to help pa­tients bet­ter tol­er­ate an­oth­er drug known for its side ef­fects.

While ear­ly da­ta from a sin­gle pa­tient aren’t say­ing much about po­ten­tial ef­fi­ca­cy, the com­pa­ny be­lieves they do of­fer key proof of con­cept for an un­ortho­dox idea pro­posed by Co­lum­bia on­col­o­gist (and cel­e­brat­ed au­thor) Sid­dhartha Mukher­jee.

Vor re­port­ed ini­tial da­ta on trem-cel back in De­cem­ber, sug­gest­ing the en­gi­neered hematopoi­et­ic stem cell trans­plant en­graft­ed nor­mal­ly in a pa­tient with acute myeloid leukemia. The biotech made trem-cel out of donor stem cells but edit­ed out CD33, an anti­gen that’s present on both leukemia cells and healthy cells. Be­cause of that, ther­a­pies that tar­get CD33 — Pfiz­er’s an­ti­body-drug con­ju­gate My­lotarg be­ing one of them — are known for caus­ing low neu­trophil and platelet counts.

“What you’re ex­pect­ing is a pre­cip­i­tous drop in platelets, some­thing in the range of even two or­ders of mag­ni­tude,” CEO Robert Ang told End­points News in an in­ter­view, which is part of why My­lotarg is on­ly giv­en every month so that pa­tients can re­cov­er.

But when Vor gave that pa­tient a low, “es­sen­tial­ly sub­ther­a­peu­tic” dose of My­lotarg, it didn’t see the side ef­fects ex­pect­ed even at this dose lev­el, ex­cept for nau­sea and vom­it­ing. And in a new da­ta up­date, the com­pa­ny said the same is hold­ing true through two more cy­cles of My­lotarg, be­fore the pa­tient was moved to oth­er treat­ments by her doc­tor and sub­se­quent­ly re­lapsed.

“We can ask a lot of ques­tions about, well, what would have hap­pened if she con­tin­ued on My­lotarg, would her dis­ease have been un­der con­trol? Maybe,” Ang said. “What would have hap­pened if she re­ceived the high My­lotarg dose? We don’t know be­cause it didn’t hap­pen.”

But the most im­por­tant take­away for the CEO is that five months in, in­ves­ti­ga­tors are still see­ing en­graft­ment of trem-cel and it ap­pears safe for the pa­tient — some­thing that Ang not­ed shouldn’t be tak­en for grant­ed. Graphite Bio, for in­stance, re­cent­ly re­port­ed a case of pro­longed low blood cell counts for a sick­le cell dis­ease pa­tient who re­ceived its gene-edit­ed stem cell trans­plant.

“Four to six months is re­al­ly crit­i­cal,” he said.

Vor has dosed a sec­ond pa­tient with trem-cel, who is see­ing both neu­trophil and platelet re­cov­ery with no un­ex­pect­ed side ef­fects. In to­tal, the com­pa­ny plans to give three pa­tients the low dose of 0.5 mg/m2, to prove that trem-cel does pro­tect pa­tients from the worst side ef­fects of My­lotarg, be­fore es­ca­lat­ing the dose.

“These are very high-risk pa­tients, and our job is to find a dose of My­lotarg in this post-trans­plant set­ting that al­lows you to keep the dis­ease un­der con­trol,” he said.

But My­lotarg, which was ap­proved 23 years ago for CD33-pos­i­tive AML, is just set­ting the stage. Vor plans to file an IND for a CAR-T ther­a­py tar­get­ing CD33 in the com­ing months, which it hopes will be even more ef­fec­tive when com­bined with trem-cel.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Lu­pus drug de­vel­op­ment mar­ket heat­ing up, while FDA links with ad­vo­ca­cy group to fur­ther ac­cel­er­ate re­search

The long-underserved systemic lupus erythematosus (SLE) market is suddenly buzzing with treatment possibilities. Less than two years after AstraZeneca’s approval for Saphnelo — the first new SLE drug in a decade and joining just one other approved in GSK’s Benlysta – the pipeline of potential drugs numbers in the dozens.

Although most are very early stage — Spherix Global Insights estimates five in Phase II/III — the pharma R&D enthusiasm is catching on among doctors, patients and advocacy groups. On Wednesday, the Lupus Research Alliance and the FDA formed a novel private-public partnership called Lupus Accelerating Breakthroughs Consortium (Lupus ABC) to help advance lupus clinical trial success.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Af­ter safe­ty re­view, EMA mir­rors FDA with up­dat­ed rec­om­men­da­tions for JAK in­hibitors

The EMA released updated recommendations today for the use of JAK inhibitors (JAKi) after reviewing data from several clinical trials that showed increased incidents of issues in certain patients who have rheumatoid arthritis and other risk factors.

The EMA noted malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality in some patients.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Mass­a­chu­setts judge dis­miss­es law­suit against Bio­gen over failed launch of Alzheimer's drug Aduhelm

A Massachusetts federal judge on Wednesday dismissed a class action lawsuit filed by investors against Biogen and several of its current and former executives over the company’s failed Alzheimer’s drug, Aduhelm (aducanumab).

The investors argued that Biogen’s contact with the FDA was unlawful and that the company made 25 false and misleading statements, including statements about the rollout and price of the drug.

Stéphane Bancel, Moderna CEO (AP Photo/Markus Schreiber)

Mod­er­na so­lid­i­fies deal with Kenya to build mR­NA man­u­fac­tur­ing fa­cil­i­ty

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

Sulagna Bhattacharya, Nanoscope Therapeutics CEO

Nanoscope’s eye dis­ease gene ther­a­py shows mixed re­sults in PhII

Dallas-based biotech Nanoscope Therapeutics unveiled Phase II results on its gene therapy for a rare eye disease Thursday morning.

In the RESTORE trial, 18 patients with retinitis pigmentosa got a gene therapy called MCO-010 while nine got placebo. On a vision test called the MLYMT, the treatment group had a one-point greater change over one year in their score compared to the placebo group, the primary endpoint of the study. However, the 95% confidence interval was 0.0 to 3.0, meaning the result was not statistically significant. The p-value was not provided.

Cedric Ververken, Confo Therapeutics CEO

Dai­ichi Sankyo inks $183M dis­cov­ery deal with GPCR biotech for CNS tar­get

Belgian biotech Confo Therapeutics has landed $183 million, plus potential royalties, in a drug-discovery deal with Daiichi Sankyo.

Early Thursday, Confo Therapeutics put out word of the deal that will be focused on small molecule antagonists to go after an undisclosed target that the company says is associated with CNS diseases.

Confo CEO Cedric Ververken told Endpoints News that Daiichi originally reached out to learn about the biotech’s technology. He added that Confo, founded in 2015, will use its platform to drug a GPCR target that Daiichi has struggled with internally.

Dif­fu­sion to hand Nas­daq spot to EIP Phar­ma for PhI­Ib de­men­tia study of ex-Ver­tex drug

One of the more than a dozen bidders for Diffusion Pharmaceuticals’ spot on Nasdaq has prevailed.

Boston biotech EIP Pharma will merge with Diffusion in an all-stock deal, with plans to start a Phase IIb clinical trial in the coming months in a common form of dementia with no approved treatments. The combined company will be renamed CervoMed.

The nine-year-old privately-held EIP is working on a former Vertex drug that it will test in a 160-person Phase IIb in patients with dementia with Lewy bodies, or DLB. The National Institute on Aging is expected to fund that trial with a $21 million grant. With the reverse merger, slated for closing in the middle of this year, EIP will be funded through that readout in the second half of 2024. EIP’s equity and debt holders will own about 77.25% of the combined company.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.