Birinapant licensing; AvantGen, IGM pairs up for anti-SARS-CoV-2 antibodies; BeiGene, Novartis to co-dvelop Tislelizumab; Valo raises USD190 M; Bluebird Bio Spins-off

Medivir, IGM Biosciences enters into an exclusive licensing agreement for Birinapant

Medivir AB has entered into an exclusive licensing agreement with IGM Biosciences to receive global, exclusive development rights for Birinapant. Birinapant is a clinical-stage SMAC mimetic that degrades Inhibitors of Apoptosis Proteins (IAPs) by binding to them, ultimately leading to cell death in tumor cells. 

Further, Birinapant also complements the anti-tumor activity of the immune system. Thus, the drug appears to be a promising therapeutic agent in treating different forms of cancer in combination with other drugs. IGM-8444 is another drug that is currently being tested in a phase I dose-escalation study in patients with solid and hematologic malignancies by IGM Biosciences. It is an IgM antibody targeting Death Receptor 5 (DR5), and IGM is hoping to test Birinapant with IGM-8444 for the treatment of solid cancers later this year. 

As per the terms and conditions of the agreement, Medivir is eligible to receive an upfront payment of USD 1 million, followed by an additional USD 1.5 million after Birinapant successfully becomes a part of the Phase I trials. Medivir is also eligible to receive milestone payments up to a total of approximately USD 350 million, plus tiered royalties up to mid-teens on net sales upon the commercial approval of the drug. 

AvantGen Enters into a Licensing Agreement for its Anti-SARS-CoV-2 Antibodies with IGM Biosciences 

AvantGen has announced the licensing of a panel of its anti-SARS-CoV-2 antibody clones to IGM Biosciences for COVID-19 therapy development. It is a panel of high-affinity human monoclonal antibody clones, which binds to two distinct epitopes on the receptor-binding domain of the SARS-CoV-2 spike protein, thereby blocking the spike protein from interacting with ACE2. This eventually averts virus-induced cell-killing, also known as cytopathic effect.

Under the licensing agreement, IGM Biosciences receives the rights to convert the antibody clones into IgA or IgM format for further development for the treatment of COVID-19. While AvantGen received an upfront payment and is eligible to receive milestone and royalty payments.

The companies believe that their candidate in its original IgG format has shown potent neutralization activity in in vitro assays and in an in vivo animal model. This will have an advantage over the multiple vaccines that have been getting EUA, which are not suitable for immunocompromised patients. 

BeiGene, Novartis partner to develop cancer drug Tislelizumab, an Anti-PD-1 Antibody 

BeiGene has announced the collaboration with Novartis Pharma AG to develop, manufacture, and commercialize BeiGene’s anti-PD-1 antibody tislelizumab in the United States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan. 

Already in markets in China, BeiGene’s Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. It is approved for classical Hodgkin’s lymphoma (cHL) following at least two prior therapies and locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression. 

The duo will jointly develop the therapy, conducting clinical trials globally. BeiGene is eligible to receive an upfront cash payment of USD 650 million, up to USD 1.3 billion upon achieving regulatory milestones, USD 250 million for sales milestones, and royalties on future sales of tislelizumab in the licensed territory. At the same time, Novartis will take care of regulatory submissions after a transition period and for commercialization upon regulatory approvals. Besides, BeiGene has an option to co-detail the product in North America, which will be funded in part by Novartis.

Valo Raises USD 190 Million in Series B Financing and Unveils Select Therapeutic Programs

Valo has announced the closing of a USD 190 million Series B financing and unveiled select therapeutic programs. The company is creating a new systemic approach for drug discovery and development. The proceeds from Series B will continue to support the discovery and development of therapeutic programs that the company is undertaking. Further, Valo plans to use the sum to advance its proprietary Opal Computational Platform and its build working capital. 

The company plans to combine its unique human-centric dataset (over 125-million patient-years) with its Opal Computational PlatformTM with an aim to leverage machine learning and patient data for the facilitated and speedy development of products at clinical stages. Some of the key preclinical programs that Valo proudly owns include NAMPT, PARP1, USP28, and HDAC3. 

The financing was led by The Public Sector Pension Investment Board (PSP Investments), along with Valo’s existing major investors, including Flagship Pioneering and several new institutional investors, including Invus Public Equities, HBM Healthcare Investments, Atinum Investment, and Mirae Asset Capital.  

Bluebird spins off to two companies, cleaving off its gene therapy, and cancer units

Bluebird bio recently announced its plans to split its genetic disease and oncology businesses. The company has decided to prioritize its severe genetic disease unit and form its oncology business into a new company.

The decision came after the company struggled to commercialize its gene therapies, and as a result, its stocks continue to stumble down. Recently, bluebird bio decided against filing for USFDA approval for its gene therapy for sickle cell disease (SCD) for at least a minimum of 2 years. 

Another of its therapy, bb1111, a LentiGlobin treatment for SCD, was building its submission on promising data from Group C pf the HGB-206 study. The company and the agency had reached an agreement on a path to transition to commercial manufacturing using an analytical comparability strategy, including a suspension-based lentiviral vector (sLVV).

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Bluebird bio to Spin Off its Oncology Business into Independent Company

Shots:

  • Bluebird plans to separate its severe genetic disease & oncology businesses into differentiated and independent publicly traded companies. The company will retain focus on SGD and will launch its oncology business (“Oncology Newco”) as a new entity
  • The spinoff is expected to result in two independent, publicly traded companies by the end of 2021
  • The spinoff is designed to unlock value through improved operational execution, organizational focus, tailored capital allocation, and enhanced strategic optionality

Click here ­to­ read full press release/ article | Ref: Businesswire | Image: Fierce Pharma

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bluebird bio to split into oncology and gene therapy specialists

US biotech bluebird bio has announced plans to split into two this year, with a separate oncology business spinning off as the company prepares to bring its products to market.

Under the plans the company’s rare disease drugs will remain under the aegis of bluebird with current genetic disease president Andrew Obenshain taking the reins as CEO.

Meanwhile the as-yet unnamed oncology company will spin off under the leadership of bluebird’s current chief executive Nick Leschly.

Leschly will also take the role of executive chair at bluebird, according to a company statement.

While bluebird has conducted pioneering work in gene therapy for blood disorders and in cancer cell therapy, products have been delayed by issues with filing data for the FDA.

Late last year, bluebird’s shares tanked after the FDA laid out additional manufacturing standards for its lead gene therapy product, Lentiglobin, in sickle cell anaemia that could hold up filing until late 2022.

Bluebird’s lead CAR-T cancer cell therapy idecabtagene vicleucel (ide-cel) was last year hit with an FDA refuse-to-file letter, which required additional data on chemistry, manufacturing and controls before reviewing the company’s dossier.

That made things difficult for development partner Bristol-Myers Squibb, which inherited the drug previously known as bb2121 through its acquisition of Celgene late in 2019.

The FDA is now due to make a decision on ide-cel as a treatment for multiple myeloma in late March.

Laying out the rationale for the spin-off, bluebird said that operating individually the two companies will be more effective at allocating capital.

The companies will be better equipped to deliver on goals and operations will be streamlined and simplified.

They will also be better at raising money with tailored investment theses and increased strategic flexibility.

The gene therapy firm will be focused on its most important therapies in beta-thalassemia, cerebral adrenoleukodystrophy and sickle cell disease in the US And Europe.

Zynteglo is already in beta-thalassemia in Europe, where the company will seek to expand access despite its hefty $1.8 million price tag.

On the oncology side, bluebird has also strengthened its board with the appointment of Dr Ramy Ibrahim, a high-profile leader in clinical development in immunotherapy and cell therapy.

Ibrahim is currently serving as a consultant for the Parker Institute for Cancer Immunotherapy (PICI) and built the clinical capabilities within the institute.

Ibrahim also worked as vice president and global therapeutic head for immuno-oncology at AstraZeneca and MedImmune, helping to develop the immunotherapy Yervoy (ipilimumab) at Bristol-Myers Squibb.

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Bluebird trumpets long-term data from beta-thalassaemia gene therapy

bluebird bio has presented long-term data from its Zinteglo one-time gene therapy for the blood disorder beta-thalassaemia, as the company continues talks with payers in Europe to bring the ultra-pricey treatment to market.

The European Medicines Agency (EMA) has granted a conditional marketing authorisation for the drug that will be marketed as Zinteglo (betibeglogene autotemcel), meaning its licence must be renewed each year until confirmatory data is available.

Results announced at the American Society of Hematology could help bluebird make the case for the long-term use of the therapy as the treatment approaches the market in Europe.

In the US, Zinteglo has hit a speed-bump with the FDA, which is asking for more information about production facilities before a review of clinical data can begin.

Of the 10 patients enrolled in the ongoing long-term study (LTF-303) from a phase 3 programme, 9/10 (90%) were transfusion independent (TI) and all these patients remain transfusion independent.

David Davidson, chief medical officer at bluebird, said: “All of the patients in our phase 3 studies who achieved transfusion independence have maintained it, with the durability of the treatment effect underscored by patients from our earlier studies reaching their five-year anniversaries of freedom from transfusions. “

In a group of patients aged under 18 from the Northstar-2 and Northstar-3 phase 3 studies, 87% (13 out of 15) achieved TI and remained so.

In a long-term follow-up 53% of patients who achieved TI and restarted iron chelation have since stopped and 30% who achieved TI now receive phlebotomy to reduce iron levels.

Davidson added: “Transfusion independence has been observed in paediatric, adolescent and adult patients and across genotypes – suggesting outcomes with this gene therapy may be consistent regardless of age or genotype.”

In Europe bluebird has set a price of up to $1.58 million euros for a single shot.

This is paid in instalments, with 315,000 euros paid up front and four additional payments due only if the treatment continues to be effective.

Zinteglo is already launched in Germany and is nearing the end of its year of free pricing.

But it’s fair to say that the therapy won’t come cheaply even though most member states will likely end up negotiating a lower price

In England, cost-effectiveness body NICE is reviewing Zinteglo and is due to publish draft document early in the new year.

Although it’s too early to say how the review will go, NICE will be looking for more certainty on the long-term effects of the therapy.

The latest data won’t be part of the submission to NICE, but the company hopes that an ongoing review of the cost-effectiveness body’s methodology will help novel gene therapies get to market.

Nicola Redfern, general manager of bluebird bio UK, is hopeful that NICE will refine its existing Quality Adjusted Life Year (QALY) and find better ways to deal with uncertainties in clinical data.

“How we deal with uncertainties is going to be fundamentally important,” she said.

Another issue to address is the discount rate NICE uses to calculate the value of medicines and their long-term impact on patients’ lives.

The 3.5% discount rate currently used means that these benefits reduce quickly over time in the view of NICE and Redfern agrees with NICE’s own proposals to adopt the 1.5% discount rate used by the Treasury.

“We agree with NICE that there is already evidence to bring it in line with the rate in the Treasury Green Book.”

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EMA starts rapid review of Bluebird’s gene therapy for rare disease CALD

Bluebird bio could be just a few months away from approval of its gene therapy for rare disease cerebral adrenoleukodystrophy (CALD) in the EU, after the EMA started an accelerated review.

If approved, Lenti-D (elivaldogene autotemcel or eli-cel) could transform the prospects of people with CALD, the most severe form of the neurodegenerative disease ALD that usually emerges in boys during early childhood and causes physical and mental disabilities as well as behavioural problems.

Around 40% of patients develop the cerebral form of ALD, which in turn affects around one in 17,000 live births.

A few weeks ago, Bluebird reported new data from the phase 2/3 STARBEAM trial of Lenti-D which showed that 87% of CALD patients were still alive and free of major functional disabilities after at least two years’ follow-up.

The EU filing comes ahead of a filing for eli-cel in the US, which Bluebird says should take place sometime towards the middle of next year, having been delayed by the coronavirus pandemic.

If approved, eli-cel would provide a one-shot treatment for CALD, holding back the progressive breakdown in the protective myelin that sheathes neurons.

It would be the first alternative to a stem cell transplant to treat the disease, a therapy that can provide significant improvements and even halt progression in some patients if given early enough.

However it requires high-dose chemotherapy to destroy the bone marrow, and that poses significant risks to patients in its own right, and can also lead to graft-versus-host disease, a potentially life-threatening complication in which the bone marrow donor’s immune cells attack the recipient’s cells and tissues.

CALD is caused by mutations in the ABCD1 gene located on the X chromosome, which provides instructions for the production of the ALD protein.

ALD protein is needed to clear toxic molecules called very long-chain fatty acids (VLCFAs) in the brain, and if mutated causes the VLCFAs to accumulate and damage the myelin sheath.

Using eli-cel, the patient’s own stem cells are modified in the lab to produce a working version of the ABCD1 gene, producing functional ALD protein that can help to flush VLCFAs from the body.

“CALD is a devastating disease, often marked by rapid neurodegeneration, the development of major functional disabilities, and eventual death,” said Gary Fortin, head of severe genetic disease programmes at Bluebird.

“If approved, eli-cel would represent the first therapy for CALD that uses a patient’s own haematopoietic stem cells, potentially mitigating the risk of life-threatening immune complications associated with transplant using cells from a donor,” he added.

Aside from STARBEAM, which will follow treated patients for up to 15 years, Bluebird is also conducting the phase 3 ALD-104 trial of eli-cel in CALD, which is due to generate results in 2024.

The EU filing for eli-cel comes shortly after Bluebird’s development partner received a 27 March 2021 FDA review date for anti-BCMA CAR-T cell therapy ide-cel, a potential therapy for multiple myeloma.

The biotech already has approval in Europe for Zynteglo, a gene therapy for haematological disease beta thalassaemia, and is due to file its related therapy LentiGlobin for sickle cell disease next year. The two therapies have been tipped to generate $1.5 billion-plus in peak sales by some analysts.

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BMS, bluebird refile FDA approval application for CAR-T therapy in myeloma

The companies’ resubmission of their application Wednesday seeking approval for idecabtagene vicleucel was in line with the timeline they provided in May, when the FDA sent a refuse-to-file letter in response to their initial submission.

BMS ‘bet’ with Celgene shareholders in balance after CAR-T refile

Bristol-Myers Squibb and bluebird bio have refiled their CAR-T therapy for multiple myeloma, leaving the outcome of a three drug “bet” with former Celgene shareholders dependent on a fast review from the FDA.

BMS gave Celgene’s shareholders a “Contingent Value Right” (CVR) to sweeten the $74 billion merger last November.

Each shareholder got one CVR that pays out $9 if three of Celgene’s pipeline drugs are approved by the FDA by certain deadlines.

The multiple myeloma CAR-T known by the name of idecabtagene vicleucel – shortened to the slightly more catchy ide-cel – must be approved by March 31 next year.

This filing for relapsed and refractory disease provides further details in a Chemistry, Manufacturing and Controls (CMC) module to address outstanding questions from the FDA, which rejected a previous submission in May.

So far only one of the drugs has been approved on time – MS drug Zeposia – and the FDA is due to make a decision on the third CVR drug, another CAR-T therapy for certain lymphomas, on 16 November ahead of a 31 December deadline.

The timetable for ide-cel is also tight: as a Breakthrough Therapy it is entitled to a faster six-month review from the FDA.

After an initial rejection in May, BMS is now relying on the FDA maintaining the drug’s Breakthrough Therapy status for it to get approved on time.

A six-month review would set up an FDA decision date in January, but a standard 10-month review would likely push a decision beyond the 31 March deadline.

There was no word from BMS on whether the FDA has granted the Priority Review – the regulator may decide that the clinical data does not support this, or it may reject the drug outright.

The impact of COVID-19 may also be a worry for holders of the CVR, which can be traded publicly under the ticker BMY-RT.

Disruption caused by COVID-19 has led the FDA to cancel several advisory board meetings, where experts provide non-binding advice to the regulator about the pros and cons of potential new drugs and therapies.

The FDA warned in May that COVID-19 could delay decisions as it prioritises resources to review potential vaccines, drugs and therapies to combat the coronavirus pandemic.

Analyst Mike Bailey told CNBC news in June that reviews of cancer drugs were unlikely to be affected – but given the many uncertainties during the pandemic this could change very quickly.

Originally codenamed bb2121, ide-cel was developed by Celgene and bluebird before the merger with BMS.

It works differently from other CAR-Ts on the market by targeting B-cell maturation antigen (BCMA), which is often found on the surface of malignant B-cells that cause multiple myeloma.

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