Category: Pharma Stocks

by Ben Adams

Canadian drug development company Deep Genomics has got off a $40 million series B round as it looks to double down on its rare genetic disease and artificial intelligence work.

Deep Genomics is one of an increasing number of biotech and drug development companies delving into AI to help better understand and create new drug targets, specifically those that have been deemed “undruggable,” as well as to design new drugs and animal models.

This approach, the company explained, results in “remarkable clarity and speed,” as, according to its figures, 70% of research projects have led to therapeutic leads, and programs have been taken from target discovery to drug candidate in less than a year.  

The $40 million swag will go toward furthering these efforts as well pushing two early-stage programs to IND this year. Deep Genomics will also be also gathering up phase 1/2 data for its Wilson disease (a rare and potentially fatal genetic disorder characterized by excess copper stored in various body tissues) candidate, slated for next year.

This series B was led by Future Ventures alongside Amplitude Ventures, Khosla Ventures, Magnetic Ventures and True Ventures.

“Therapeutically re-engineering the human genome is the final frontier,” said Brendan Frey, founder and CEO of Deep Genomics. “Doing so requires systems that can predict information pertaining to the genome, and the best technology we have for prediction is AI. We have found that the more we explore the universe of genetic therapies using AI, the more we discover dark regions that can be illuminated only with the development of new technology.

“This financing will enable us to expand our AI technology in the pursuit of new therapeutic opportunities, to advance our Wilson program into the clinic, and to strategically partner assets emerging from our overflowing preclinical pipeline.”

RELATED: In conversation with Brendan Frey: Deep Genomics reveals the first-ever AI-discovered drug candidate

The Toronto-based biotech has been quietly plugging away since 2015 on its AI Workbench. It uses more than 20 machine learning systems that have been “carefully validated and tested” and trained on public and proprietary data to screen disease-causing mutations in search of new drug targets.

“We have built a system that within two hours can scan over 200,000 pathogenic patient mutations and automatically identify potential drug targets,” Frey told FierceBiotech last fall. Instead of chasing known targets or getting into a hot therapeutic area, Deep Genomics is letting the system do the choosing—an approach that saw it land on Wilson disease.

Deep Genomics’ system figured out that a mutation changes an amino acid in ATP7B, a copper-binding protein that is absent in Wilson patients. But it also predicted that this change should not affect how the protein works. The AI eventually discovered that the mutation disrupts an instruction in the genome that tells cells how to make that protein, causing it to not be made at all.

The platform identified a dozen potential drug candidates, and Deep Genomics took them to the lab to make sure they worked the way the AI predicted they would. After some tolerability and pharmacokinetics experiments, the company declared DG12P1 its first pipeline candidate that it would advance toward IND.

“For over twenty years, our team at Future Ventures has backed visionary companies seeking to change the world for the better,” said Steve Jurvetson, co-founder of Future Ventures and board member of Tesla and SpaceX.

“Deep Genomics has pioneered a better way to systematically discover new therapies with a much higher success rate than traditional pharma methods. My partner Maryanna Saenko and I are excited to be joining them on a journey to modernize drug development by using AI to design and de-risk drug development programs up front, instead of relying on trial-and-error experiments that are fraught with time delays and high cost.”

by Nick Paul Taylor

Novo Holdings has changed the scope of its REPAIR Impact Fund to enable it to bankroll antibiotics for longer. REPAIR began life focused on projects between lead optimization and phase 1, but, in light of the tough funding environment for anti-infectives, will now support programs into phase 2.

Denmark’s Novo, the holding company for Novo Nordisk, set up the $165 million (€147 million) fund two years ago to provide early-stage funding for drugs and vaccines against resistant microorganisms. The focus reflected a belief that a funding gap existed between lead optimization and phase 1. Now, having invested $48 million in eight companies, Novo has identified a later-stage funding problem.

Aleks Engel, director of REPAIR fund, outlined the gap and his response to it in a statement: “Based on experiences to date, we may slow down our early investments slightly in order to potentially advance projects further.”

In practice, that will mean REPAIR keeps some money back to support phase 2 trials run by some of its portfolio companies. Without support from REPAIR, the fund’s portfolio companies could struggle to raise money for phase 2 trials if other investors divert money away from the sector in response to the commercial difficulties faced by companies such as Achaogen and Melinta Therapeutics.

Even after the change in focus, the period between lead optimization and phase 1 remains the sweet spot for REPAIR. The fund began 2020 by unveiling investments in two more biotechs with programs in that sweet spot.

REPAIR invested €7 million in Mutabilis, a French biotech that is currently putting a wide spectrum Gram-negative anti-infective agent through lead optimization. The other investment funneled $3.9 million to Maryland-based IBT Vaccines to fund work on a preclinical-stage Staphylococcus aureus vaccine.

by Ben Adams

Last year, we asked: Are too many early-stage biotechs going for IPOs, and when will the bubble burst?

Cancer upstart Black Diamond Therapeutics has paid no mind to this, and just over a year after its series A raise is going for a $100 million IPO.

It’s been a whirlwind 12 months, with two quick-fire raises coupled with a series of big-name execs coming to the biotech, which nabbed Yumanity, Merck KGaA and SR One veterans back in September to help head up its research work.

This trio of new research leads are Christopher Roberts, Ph.D., chief scientific officer; Matt Lucas, Ph.D., vice president of chemistry; and Tai-An Lin, Ph.D., VP and head of biology.

Roberts oversees all of Black Diamond’s research and early development. Lucas will run its chemistry work in Cambridge, Massachusetts, while Lin is heading up its labs in New York.

The new CSO comes to the biotech from SR One, the corporate venture capital arm of GlaxoSmithKline, where he was an entrepreneur in residence. Lucas, meanwhile, was the senior director of chemistry at Parkinson’s disease biotech Yumanity Therapeutics.

Lin has been director of the immuno-oncology translational innovation platform and experimental medicine at Merck KGaA/EMD Serono, with stints before this on a series of Big Pharma drug discovery teams at Bristol-Myers Squibb, Roche and Janssen.

The Versant Ventures biotech raised $85 million in a series B at the start of the year, coming just weeks after Black Diamond exited stealth mode. It broke cover with a $20 million in series A and a platform designed to identify and target allosteric mutant oncogenes.

Together, these cash grabs teed up the allosteric oncogenic mutation specialist up to move two or three candidates into the clinic in the coming years: It now wants an extra $100 million from the public markets to help in this mission.

The biotech’s founders David Epstein and Elizabeth Buck designed the platform to unlock the therapeutic potential of oncogenes activated by allosteric mutations, which, unlike kinase domain mutations, are yet to make a mark on cancer care.

If the platform works as Black Diamond hopes, it will generate single molecules capable of treating baskets of mutations previously seen as unactionable from a therapeutic perspective.

The company is now focused on getting its lead program, BDTX-189, into the clinic to test this platform. According to its Securities and Exchange Commission filing, the biotech submitted its IND for BDTX-189 in November 2019, which got the FDA green light a month later.  

Black Diamond is plotting a combined phase 1/2 clinical trial in the first half of 2020. “The Phase 1 portion of the trial will evaluate escalating doses of BDTX-189 and is designed to determine the recommended Phase 2 dose and to assess preliminary indications of anti-tumor activity,” it said in the filing.

“The Phase 2 portion will determine the objective response rate, or ORR, and duration of response in patients with solid tumors that have an allosteric HER2 mutation or EGFR or HER2 exon 20 insertion mutation determined using next-generation sequencing, or NGS. Depending on results, we plan to pursue an accelerated approval of BDTX-189 for a tumor-agnostic indication in patients with mutations of the ErbB family.”

It’s also working on a preclinical candidate that it hopes can combat glioblastoma, a particularly aggressive form of brain cancer with few treatments and poor outcomes.

For this candidate, Black Diamond said: “Our lead molecules are designed to be potent, allosteric EGFR selective and to be brain penetrant. We have observed measurable brain exposure in animal models. We are completing preclinical characterization of our glioblastoma candidate leads and plan to select a development candidate in 2020.”

The Cambridge, Massachusetts-based company plans to list on the Nasdaq under the symbol “BDTX.”

by Angus Liu

An abnormality in the SOD1 gene is linked to some inherited cases of amyotrophic lateral sclerosis (ALS). So could turning off the mutated gene halt the disease? An international research team led by the University of California San Diego School of Medicine showed the potential of that strategy in mice by using a gene therapy approach.

A one-time injection of a gene-silencing RNA delivered by an adeno-associated virus (AAV) vector into the spinal cord prevented the onset of ALS in presymptomatic mice, and it blocked disease progression in rodents that had already developed symptoms. The team reported the findings in the journal Nature Medicine.

The SOD1 gene codes for an enzyme called superoxide dismutase. Normally, the enzyme breaks down superoxide radicals that are produced during cell metabolism. But in ALS, SOD1 mutations can create misfolded SOD1 protein, as toxic oxygen molecules persist, leading to the death of motor neurons.

The UC San Diego-led team postulated that a short hairpin RNA (shRNA)—an artificial RNA molecule that can silence gene expression—could be utilized to block the dysfunctional SOD1 gene.

Other researchers had tried delivering shRNA-bearing vectors into the blood via intravenous injection. In mouse models of ALS, disease progression was indeed slowed, but the approach only extended survival by about three months. In a more recent study, scientists used intrathecal injection into the cerebrospinal fluid, but the animals lived only two months longer despite being treated immediately after birth. 

For the current study, the UCSD researchers injected the shRNA-containing AAV therapy into the spinal subpial space at cervical and lumbar spine levels.

The team observed impressive results. Remarkably, SOD1-mutated mice treated before disease onset never developed disabilities related to motor neuron functions when followed to an average age of 462 days. That means they didn’t lose functions like grip strength or orientation reflexes. The control animals, by contrast, started showing symptoms at about 306 days and reached the end-stage of ALS about three months later.

Further analysis showed that the therapy suppressed the accumulation of misfolded SOD1 protein and almost completely preserved motor neuron cells.

In mice that had already entered the symptomatic stage, the injection also blocked disease progression and further motor neuron degeneration, the team reported.

“At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutated SOD1 gene-linked ALS,” the study’s senior author, Martin Marsala of UCSD, said in a statement.

RELATED: Biogen’s antisense ALS drug shows promise in early clinical trial

Several other strategies have been developed aimed at decreasing the production of mutated SOD1 protein. Swiss biotech Neurimmune has a recombinant antibody called α-miSOD1, which the company developed based on memory B cells that are found in healthy elderly people and that protect against misfolded SOD1. In mouse models of ALS, the drug extended the animals lives by up to two months.

Antisense oligonucleotide therapy is another potential modality for fighting neurodegenerative disease. Biogen recently showed its antisense drug tofersen (BIIB067) was well tolerated in ALS patients in a small phase 1 study. At its highest dose, the drug cut SOD1 protein levels in spinal fluid and the patients performed well on certain clinical function tests.

Marsala and colleagues now plan to run additional studies of their spinal subpial shRNA approach in a large animal model to determine the optimal, safe dosage of the treatment.

“In addition, effective spinal cord delivery of AAV9 vector in adult animals suggests that the use of this new delivery method will likely be effective in treatment of other hereditary forms of ALS or other spinal neurodegenerative disorders that require spinal parenchymal delivery of therapeutic gene(s) or mutated-gene silencing machinery, such as in C9orf72 gene mutation-linked ALS or in some forms of lysosomal storage disease,” Marsala said in the statement.

by Nick Paul Taylor

Novan’s antiviral SB206 has failed to beat placebo in two phase 3 trials in patients with molluscum contagiosum. The setback wiped 74% off Novan’s value and left its cash runway looking precariously short, but the biotech plans to start another trial in the belief it still has a path to approval.

SB206 is made up of a hydrogel and a gel containing berdazimer sodium. Co-administering the two components is intended to promote the release of nitric oxide, a small molecule with antimicrobial properties. Novan has built a pipeline around nitric oxide that is spearheaded by two phase 3 trials designed to assess the effect of SB206 on viral skin infection molluscum contagiosum.

The two trials enrolled about 700 participants in total and randomized them to apply SB206 or a topical placebo once a day. After 12 weeks, investigators assessed whether treatable molluscum contagiosum remained on the patients.

SB206 was statistically no better than placebo at fully clearing molluscum contagiosum in either trial, resulting in both studies missing their primary endpoints. That headline failure sent Novan’s stock into a tailspin.

However, Novan had a more positive take on the data, noting that, with a p-value of 0.062, one of the trials approached statistical significance. Tweaking the primary endpoint population, either by taking a per protocol approach or by changing the handling of missing data, brought the p-value down to below the threshold for statistical significance. 

Coupled to a positive result against a secondary endpoint that looked at the clearance rate at week eight, Novan thinks the analyses are encouraging enough to warrant using the data in a filing for FDA approval. The second clinical study failed to generate good enough data for it to serve as the second confirmatory trial. Yet, Novan thinks the second study’s findings are “consistent with and supportive of” the more encouraging trial. 

That upbeat reading of the data set led Novan to outline plans to start another phase 3 trial in April. If that study generates positive results, Novan will use it as the second confirmatory trial and file for FDA approval in 2021. 

While that is what Novan wants to do, there are doubts about whether it will be able to execute the plan. The plan is dependent on feedback from the FDA and the willingness of investors to give Novan more money. Novan closed out September with $22.5 million in the bank, a sum that will only fund its operations into the first quarter of 2020. Investors diminished Novan’s ability to raise money after getting a look at the phase 3 data by sending its stock price down 74% in after-hours trading. 

by Nick Paul Taylor

Melinta Therapeutics has filed for Chapter 11 bankruptcy. Deerfield is set to take control of Melinta as payment for the $140 million loan it extended to the antibiotics business.

New Jersey-based Melinta sounded the alarm repeatedly in 2019, warning investors of doubts about its ability to continue as a going concern in May and stating in November that the situation was likely to come to a head in the next few months. Faced with a bleak financial situation, Melinta has put together a restructuring agreement designed to put it on sounder fiscal footing. 

The agreement will see Deerfield receive 100% of the equity issued by the reorganized company. To facilitate the agreement, Melinta is seeking Chapter 11 protection. Melinta is set to lay off about 60 people in conjunction with the reorganization. 

Earlier efforts by Melinta to improve its financial performance also cost people their jobs but failed to keep the company out of bankruptcy. Jennifer Sanfilippo, the latest in a succession of people to hold the CEO title at Melinta, thinks this time will be different. 

“We are confident that this process will secure new ownership of the business with the financial resources to support the company’s antibiotics portfolio and ensure these potentially life-saving products continue to get to patients in need,” Sanfilippo, Melinta’s interim CEO, said in a statement. 

Melinta’s filing for bankruptcy capped off a bleak year for the antibiotics industry. Aradigm and Achaogen filed for bankruptcy in the first half of the year, despite the latter company winning FDA approval for an antibiotic in June 2018.

That series of bankruptcy filings, which featured two companies with commercial products, will add to fears that the antibiotics business model is broken. Some investors and biotechs retain an interest in the sector—Brii Biosciences, for example, is spending some of its $260 million fundraising haul on antibiotics R&D—but other therapeutic areas have a far better track record of delivering a return on investment. 

by Arlene Weintraub

CD40, a receptor on the surface of immune cells, has long been of interest in oncology research because activating it stimulates cancer-killing T cells. Several companies have developed antibody drugs targeting CD40, including Roche, but they’ve proven disappointing on their own in clinical trials.

Scientists at the University of Basel say they may have found a way to improve responses to CD40 antibodies. They combined a CD40 drug with two other antibodies that are anti-angiogenic, meaning they plug up leaky blood vessels that feed tumors. The combination accelerated tumor destruction in mouse models of several cancers, including breast, colon and skin cancers, they reported in the journal Proceedings of the National Academy of Sciences.

“Normally, the blood vessels of a tumor are leaky or stunted. Therefore, there is no good way for killer T-cells to get inside,” explained lead author Abhishek Kashyap of the University of Basel in a statement.

Kashyap’s team collaborated with scientists at the Roche Innovation Center to test three of the company’s drugs in combination. They were Avastin, Roche’s blockbuster anti-angiogenic cancer treatment that blocks VEGF, and two experimental drugs: one targeting another anti-angiogenic molecule, Ang2, and the second aimed at CD40.

The two anti-angiogenic drugs stabilized the blood vessels surrounding the tumors, improving the flow of killer cells that attacked the cancer, the researchers reported. But the triplet also seemed to turn “cold” tumors “hot,” meaning the drugs changed the microenvironment in a way that made the cancer more vulnerable to immunotherapy.

RELATED: AACR: Apexigen, BMS steal the show with promising I-O combo in pancreatic cancer

Several clinical trials investigating the potential of CD40 combination treatments are already underway. Apexigen’s APX005M combined with chemotherapy and Bristol-Myers Squibb’s anti-PD1 blockbuster Opdivo has shown promise in early clinical trials in pancreatic cancer, for example. Apexigen is also testing a combination of APX005M, Opdivo and cabiralizumab, an anti-CSF-1 antibody that BMS and Five Prime Therapeutics are developing.

Roche is testing its CD40 drug, selicrelumab, with its anti-PD-L1 drug Tecentriq in solid tumors. It’s also investigating combining selicrelumab with either Avastin or vanucizumab, a bispecific antibody that targets both VEGF-A and Ang2.

The new study led by the University of Basel concluded that the key to targeting CD40 successfully in cancer “is likely to be realized in combination with other, nonredundant immune modulators,” the researchers wrote. “We consider our findings useful in the light of current early-phase clinical studies that investigate agonistic anti-CD40 antibodies in combination with various antiangiogenic agents.”