Novo backs ‘breakthrough’ antifungal player’s $60M round with a focus on rare mold infections – Endpoints News

The plight of antibiotics developers has been well documented: chronically underfunded research, daunting scientific challenges, and little commercial upside even for the ones that make it to the market. But in an adjacent corner of the antimicrobial space, an antifungal player is out to paint a very different picture.

F2G, a UK-Austria hybrid, has raised $60.8 million for its final push toward the clinic. Clearing the test could pave the way for its drug to be the first new antifungal agent in 20 years.

Thats how sparse the landscape has been, CEO Ian Nicholson told Endpoints News.

Its not for the lack of need, Nicholson noted. Much like in the antibacterial space, antifungal resistance is common occurring in 30% of patients taking the mainstay triazoles. Left untreated, the mortality rates for some of these rare mold infections targeted by F2G can be between 90% and 100%. Because fungi are eukaryotes just like humans, it has been difficult to discover new targets and corresponding new chemical entities.

The biotech began as a spinout of the University of Manchester, tapping into technologies that enabled them to manipulate and analyze fungal genes. F2G scientists eventually zeroed in on DHODH or dihydroorotate dehydrogenase, a key enzyme that helps fungi create the building blocks it needs to grow.

As it turned out, this blockade also kills the fungus. Out of this new class of antifungals dubbed orotomides, the lead candidate olorofim has been designated a breakthrough therapy (a first for antifungals, according to Nicholson), an orphan drug as well as a qualified infectious disease product. The ongoing open label Phase IIb study is testing it in a variety of rare mold infections, including invasive aspergillosis, scedosporiosis, lomentosporiosis, fusariosis, scopulariopsosis and coccidioidomycosis (valley fever).

For the upcoming Phase III, though, F2G plans to focus solely on invasive aspergillosis where a single study involving a couple hundred patients is expected to cement approval.

Valley fever is also a top priority in the US, where CMO John Rex, the former head of infection at AstraZeneca, leading a clinical team.

Compared to bacterial infections, fungal infections typically need to be treated for much longer, a matter of months rather than days. Theres no abundance of cheaply priced generics, and payers that F2G has talked to agreed that any new entrants should be priced relatively high.

Its a similar therapeutic area, but in many respects commercially it is much more like a rare disease drug than conventional anti-infective drug, CFO Ralf Schmid said.

Citing Gileads AmBisome as an example and an entrenched rival, Schmid pointed out the drug can cost $1,400 per day despite the availability of generics.

Just to set the context, added Naveed Siddiqi, a partner at Novo Ventures, the big drugs in the states are voriconazole and propiconazole, and they both at peak sold somewhere between $700 million and over $800 million.

Novo came on board for the first $60 million round back in 2016. Morningside Ventures, another existing investor, stepped up for the new funding alongside Brace Pharma Capital, Advent Life Sciences and new backer Cowen.

In addition to funding the clinical trial, the financing is also expected to scale up the current 20-person team in preparation for launch. Nicholson said the growth will be substantial but dont expect it to match the pharma rivals.

Because these infections occur in the context of transplants or cancer, when theyre immunosuppressed, a small company with a relatively limited salesforce and commercial organization can actually address this, Siddiqi said.

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Novo backs 'breakthrough' antifungal player's $60M round with a focus on rare mold infections - Endpoints News

CanSino reaps $748M windfall from Shanghai IPO as it warns Covid-19 vaccine won’t be a huge money maker – Endpoints News

CanSino began the year with a clear goal to secure a secondary listing on Shanghais STAR market. Then something more urgent came along: As a rising vaccine developer on a mission to bring global standard immunizations to China, it heeded the call to make a vaccine to protect against a virus that would paralyze the whole world.

Xuefeng Yu and his team managed to keep doing both.

More than a month after CanSinos Covid-19 vaccine candidate is authorized for military use in China, the Hong Kong-listed company has made a roaring debut in Shanghai. It fetched $748 million (RMB$5.2 billion) by floating 24.8 million shares, and soared 88% on its first trading day.

At RMB$209.71 apiece, its the second most expensive IPO ever on the nascent tech board, according to the South China Morning Post.

In opening the STAR market last year, Shanghais stock exchange followed its Hong Kong counterparts footsteps. By lowering the listing requirements to accommodate pre-revenue tech and biotech companies, both bourses are looking to lure domestic upstarts back from Nasdaq.

Its not uncommon for STAR stocks to jump dramatically or even double upon their debuts. In fact, CanSino closed at a lower price than expected.

The first-day gain turned out to be smaller than traders expected because of worries about frothy valuations on the overall A-share market, Ivan Li, a money manager at Shanghai-based Loyal Wealth Management, told SCMP. But investors still have confidence in the stock and its vaccines in the pipeline.

Covid-19 has delayed clinical plans for its earlier-stage vaccines, CanSino reported in its prospectus, which are candidates designed to protect against pneumococcal diseases as well as diphtheria, tetanus and pertussis.

Meanwhile, logistical troubles are still stalling the plan to test the coronavirus vaccine, Ad5-nCoV, in Canada. With political tension and speculation running high, CanSino has turned to Saudi Arabia to kick off its first Phase III test like all the other Chinese vaccine makers, its opting to do late-stage studies in places where infections are still widespread.

Even if the Phase III results are positive, though, dont expect it to be a money maker. CanSino noted that the Chinese government might be taking control of pricing and supply as well as exports, leading to a lower profit margin than other products.

An Ebola vaccine developed with a scientist from Chinas army whos also a collaborator on the Covid-19 program remains the only approved product in CanSinos portfolio. Two meningococcal vaccines are now under regulatory review.

The company wrote that its building a sales and marketing team, with the goal being to expand from the current 20-plus to 100 by the end of 2020.

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CanSino reaps $748M windfall from Shanghai IPO as it warns Covid-19 vaccine won't be a huge money maker - Endpoints News

Roche pulls a tumor micro-environment drug out of the freezer, hands it to a UK upstart – Endpoints News

Two years after pulling it from clinical development, Roche has handed control of a solid tumor cancer drug to a tiny Oxford University spinout.

For an undisclosed fee, Celleron Therapeutics acquired the drug, an anti-CSF1R antibody thats designed to modulate the tumor micro-environment an increasingly popular approach among cancer drug developers. Celleron says it will now put the drug into trials for patients with tenosynovial giant cell tumors, a rare disease where series of benign tumors begin to grow around the joints and tendons. Its caused by cells over-producing CSF1R.

The deal appears to be a straight biotech-repurposing-off-the-Pharma-shelf deal. Although Roche launched 4 different trials for the drug one of which is still technically on-going the Swiss pharma retired the drug as part of a broad pipeline sweep back in October of 2018. It was a business decision, the company wrote on one withdrawn studys page on clinicaltrials.gov, stipulating there were no safety or efficacy concerns.

In fact, the antibody had looked promising in the only efficacy results that ever surfaced. In a Phase I study published in The Lancet Oncology, 24 out of 28 patients responded to the drug, and two of them had a complete response.

Celleron will now have a chance to test whether those results can bear out in larger trials. The company says its built a proprietary platform around epigenetic control and immune modulation, but most of their clinical efforts so far have focused on an in-licensed drug from AstraZeneca that inhibits histone deacetylase, a class of enzymes that change one of the types of epigenetic markers on DNA. Theyve put it into Phase I and Phase II trials in the UK and in China in different combinations and different cancers, including T-cell lymphomas and HCC.

Still, Celleron has its own assets, including a series of preclinical assets that target histones. They also have CXD201, a molecule that inhibits topoisomerase, one of the enzymes that winds and unwinds DNA. And they say they use biomarker data to match the best drugs to the best patients.

The company has never announced how much capital theyve raised, but they said in 2017 they raised funding from a South Korean consortium.

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Roche pulls a tumor micro-environment drug out of the freezer, hands it to a UK upstart - Endpoints News

Avobis Bio and Vineti announce strategic collaboration to support new implantable cell therapies addressing debilitating conditions – GlobeNewswire

August 11, 2020 09:00 ET | Source: Vineti

NEWARK, Del. and SAN FRANCISCO, Aug. 11, 2020 (GLOBE NEWSWIRE) -- Today, Avobis Bio, LLC (Avobis Bio), a clinical-stage regenerative therapy company specializing in the development of implantable cell therapies, and Vineti, Inc., the leading software platform for personalized therapeutics, announced a new collaboration to advance and scale Avobis Bios innovative cell therapy pipeline.

Avobis Bios first therapeutic involves harvesting and processing a patient's own mesenchymal stem cells for the treatment of perianal fistulas, an often debilitating condition that afflicts patients with Crohn's disease. Personalized therapies require a software system to manage the complex value chain associated with autologous, patient-based therapies and Vineti provides the leading digital software platform to align and efficiently manage this process.

Avobis Bio is working towards a major leap forward in implantable cell therapy for treating debilitating conditions and alleviating patient suffering, said Tiffany Brown, General Manager, Avobis Bio. Our clinical-phase pipeline will advance more quickly with the support of a leading software platform that solves many of the infrastructure challenges facing personalized treatments.

Through this collaboration, Vinetis software platform will help Avobis Bio advance its clinical trial by supporting cell collection scheduling, logistics orchestration, and traceability for each patients individual drug product.

Vinetis Personalized Therapy Management platform (PTM) is the first cloud-based software platform to help safely and efficiently move patient-based personalized therapies through clinical development and into mainstream medicine at scale. The Vineti platform configurable, cloud-based, secure and scalable brings the best of enterprise software to advanced therapies. The Vineti solution automates traceability for personalized therapies, enables sophisticated, efficient treatment scheduling and manufacturing, and helps ensure conformation with regulations and standards.

Vineti is honored to support Avobis Bio in its work to develop a new generation of implantable cell therapies, said Amy DuRoss, CEO and Co-founder, Vineti. Avobis Bio has created a remarkable new approach for patients in true need. We are very excited to help them scale their treatments and reach more patients with few other options.

About Avobis Bio, LLC

Avobis Bio is dedicated to advancing the development of implantable cell therapies to treat debilitating conditions without a cure. The investigational portfolio explores the use of mesenchymal stem cells combined with bioabsorbable scaffolds to enhance the effectiveness of cells in stimulating the body to heal. Avobis Bio was formed as a joint venture between Mayo Clinic and W. L. Gore & Associates to combine capabilities in clinical care, cell biology, materials science and commercialization of medical products. In a tribute to the patients it serves and the power of their own mesenchymal stem cells, Avobis Bio draws its name from the Latin a vobis, meaning from you or by you.

About Vineti, Inc.

Vineti is the first commercial, configurable cloud-based platform to expand patient access to life-saving cell and gene therapies. Vineti was co-founded by GE and the Mayo Clinic to solve the key challenges that patients, medical providers, biopharmaceutical companies and regulators face in the delivery and commercialization of individualized therapies. Now a fully independent company, Vineti offers a digital Personalized Therapy Management (PTM) platform of record to integrate logistics, manufacturing and clinical data for personalized therapies. The Vineti platform supports the full continuum of patient-specific therapies, including cancer vaccines and autologous and allogeneic therapies. The company is expanding rapidly, and the Vineti platform will be in use in hundreds of leading medical centers worldwide in 2019, on behalf of multiple biopharmaceutical partners. In 2019, the World Economic Forum selected Vineti as a global Technology Pioneer.

Media Contacts

Vineti Stacy Henry press@vineti.com

Avobis Bio, LLC Paul Fischer information@avobisbio.com

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Avobis Bio and Vineti announce strategic collaboration to support new implantable cell therapies addressing debilitating conditions - GlobeNewswire

Plotting to be the BridgeBio of AI, Atomwise lands $123 million Series B for hype-heavy platform – Endpoints News

The PR-friendly, well-partnered AI biotech thats provoked stern skepticism in some scientific corners is getting a boatload of new cash.

Atomwise has announced a $123 million Series B round led by Sanabil Investments a subsidiary of the Saudi royal fund and B Capital Group and joined by DCVC and Y Combinator, among others. The new round is nearly triple what Atomwise had raised prior and will go towards both scaling their molecule-hunting software and building the growing network of spinouts theyre launching to develop some of the molecules that software has turned up.

The goal ultimately, said CEO Abe Heifets, is to build a portfolio of smaller biotechs beneath theirs a kind of BridgeBio for AI.

We want to grow in scale, Heifets told Endpoints News. The technology is small molecule thats a very broad umbrella so theres increasingly an interest in a portfolio approach

The round could be a legitimating one for Atomwise, a company that over the last few years has found itself at the center of a debate between engineers who promised that machine learning and AI networks could remake drug development and scientists who saw a lot of buzz but little substance. Since its days at Y Combinator, the company has promised to use an AI convolutional network to rapidly screen billions of molecules for their ability to hit a target or bind to a protein, and in doing so speed from years to days the process of selecting drug candidates. In doing so, they said, they could cut short the arduous and expensive drug development path.

The problem, critics such as science blogger and medicinal chemist Derek Lowe argued, is that it just doesnt take that long to screen molecules. Its a bump in the drug discovery mountain.

You can do a million in six weeks. The whole compound screening step is just another early thing in preclinical space, Lowe wrote in one piece that also noted Atomwises tendency toward overstatement.

Ive never seen a successful project in which it was a rate-limiting step. But shave a few weeks off something at the very beginning isnt as compelling an offer, is it? he said.

Though just one of many companies now offering rapid, AI-enabled screening, Atomwise might be the most prolific, claiming over 750 research collaborations addressing over 600 disease targets and partnerships with major pharma companies, including Eli Lilly, Merck, Koreas Hansoh Pharmaceuticals, Bayer and BridgeBio.

Yet it has advertised those big-name partnerships with particular fanfare. Rather than calculate the overall potential deal value by upfront fees and milestones, as most biotechs do, they have often listed values that include royalty estimates based on historical average revenues for small molecule drugs with success in all projects in an industry where success is fleetingly rare. Thats allowed the company to advertise that Atomwise has signed more than $5.5 billion in total deal value with corporate partners to date without disclosing any individual payments.

Heifets says that their deal releases are in line with how other biotechs talk about their deals and what their partners are willing to disclose. He also says Atomwise provides benefits beyond that initial screening step.

If you think of AI as only being applied for high throughput screening, then I agree with Derek, he said. Thats a beginning part and thats pretty quick.

Heifets said that Atomwise also provides services for lead optimization, a longer and more difficult step. And he said that theyve shown the software can not only find molecules faster but also find molecules for targets that major companies have spent years and millions of dollars failing to hit.

Most notably, Atomwise launched X-37 last year in part around the discovery of molecules that can bind to the PIM3 pathway without harming healthy tissue, which Heifets said Roche, Novartis and AstraZeneca had tried and failed to do. The company raised $14.5 million in Series A funding. They also quietly launched Theia Biosciences around molecules that can hit theHTRA1 pathway and might be used to treat age-related macular degeneration.

Over the next few years, Heifets said, they plan to launch more biotech subsidiaries, hopefully eventually putting multiple drugs in the clinic. If the markets keep their historic pace, he said, an IPO could also be in their fortunes.

That would likely mean a hefty S-1 and another round of arguments over the role of AI in biotech, and whats hype and whats reality.

I think that will depend on what the markets are doing, Heifets said. There have been a number of very successful IPOs recently in the biotech sector, so its a very interesting time.

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Plotting to be the BridgeBio of AI, Atomwise lands $123 million Series B for hype-heavy platform - Endpoints News

Strategies and Suggestions for Patent Applications in the Hot Field of Biotechnology – Lexology

Abstract: The field of biotechnology is growing rapidly and the number of patent applications is skyrocketing. CAR-T, gene editing, and coronavirus vaccines have become hotspots due to their extremely high clinical value or due to epidemic outbreaks. Because of complex ethical issues, the rapid development and the unpredictability of biotechnology, there is particularity existing in the field of biotechnology, which means the policy and criteria of examinations are frequently changing. It would be very helpful for the applicant (or the patentee) to understand the dynamic changes in the examination criteria in the field timely and accurately, so that they can obtain and maintain their patent rights and protect their legitimate rights and interests successfully. This article analyzes the dynamic changes of examination in this field from three angles sufficiency of disclosure, supportiveness of claims and inventive step, and further provides some strategies and suggestions based on these analyses.

Keywords: biotechnology, gene editing, CAR-T, coronavirus, vaccine, sufficiency of disclosure, supportiveness of claims, inventive step

Introduction

In recent years, there have been plenty of breakthroughs in medical applications of the biotechnology field. Cell therapies represented by CAR-T and monoclonal antibodies against PD-1 have been very successful and approved for clinical use. The discovery of some advanced gene editing tools also brought on the dawn of the area of gene therapy. These breakthroughs are the current hotspots in the field of biotechnology. The huge market share is attractive for investment in research and development to large domestic and international traditional medical companies as well as newly rising companies. The outbreak of epidemics seriously threatens human life and health. As the most effective way to defeat the malignant infectious diseases, the development of vaccines is urgently required. Although the primary purpose for developing vaccines is to protect human life and health, the potential for huge commercial profits cannot be ignored. Regardless of what the starting point is, vaccines, particularly vaccines to prevent coronavirus that can cause severe respiratory infections, have become another hotspot for research and development. Nowadays, the rapid development of biotechnology has profoundly affected and changed all aspects of human life. Biotechnology has become the focus of international technological and even economic competition.

A mature and comprehensive patent system should be used to fuel to the rapid and healthy development of the biotechnology field. The patent system repays the research and development investment of innovative entities with market share through the protection of research and development results, thereby further stimulating the enthusiasm of scientific research and encouraging innovation. Despite the rapid development of biotechnology, the continuous emergence of scientific discovery, the improvement of the Chinese patent system, and the increased protection of intellectual property rights, it is necessary to master the dynamic changes in patent examination in China and ensure that scientific achievements are protected appropriately by patents in order for inventors to take full advantage of this system.

Based on patent examination data and typical cases, we analyze the current situation on patent application and examination in the biotechnology field, especially in some hotspots areas, and provide strategies and suggestions on patent application and protection based on this.

Data-based analyses on current situation of Chinese patent applications and examination

In the past two decades, with the rapid development of biotechnology, the number of patent applications in this field in our country is rapidly increasing. In particular, when a technological breakthrough with significant medical or other applications is made, or when prevention/treatment or drugs are urgently needed, such as in the case of an epidemic, patent applications always surge.

1 The situation of patent application and examination in biotechnology in China.

Figure 1

Since 2001, the number of patent applications in biotechnology in China has shown a trend of linear increase. The number of published patent applications so far is about 270,000 (the decline in the number of applications in 2019 and 2020 is due to a large number of applications that have not yet been published and so no data is available). The estimated number of applications in 2019 should exceed 30,000, and it is estimated that the number of applications in 2020 may reach about 32,000 (see Figure 1).

Looking at the current situation of patent examinations in the field of biotechnology, we find that the status of a large number of patent applications since 2015 in the field of biotechnology have not yet been finalized (68.54%). Among the finalized patent applications, valid patents account for 59.7% and invalid patents accounted for 40.3%. Because of the low rate of abandonment within 5 years, the invalidity mainly resulted from rejection or withdrawal. Therefore, it is estimated that the grant rates of patent applications in the biotechnology field from 2015 to present is about 60%.

About 2.44% of all patent applications in the field of biotechnology have been rejected and entered the Review procedure. Among these, 48.69% are maintained to be rejected and 51.31% rejections are withdrawn; approximately 0.07% of the applications were challenged and found to be invalid after patent rights were granted. Among these, 42.83% are completely invalidated, 21.84% are partially invalidated, and 35.24% remained valid.

2 Current situation of CAR-T related patent applications and examinations

In 2007, immunologist Michel Sadelain first proposed Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T). In recent years, due to its remarkable effectiveness, it has been recognized by the industry and large pharmaceutical companies started the research and development of new cell therapy. On July 31, 2017, Novartiss gene therapy product-CAR-T cell drug Kymiriah (tisagenlecleucel, CTL019) was approved by the US FDA. The drug is used to treat relapsed or refractory B-cell acute lymphoblastic leukemia in children and adolescents. This has become another milestone in the field of cancer immunotherapy after Anti-PD-1 drugs. Later, on October 18, 2017, the US FDA approved Yescarta (axicabtagene ciloleucel, KTE-C10) of Kite Pharmaceuticals. This drug is used to treat adult patients with specific types of large B-cell lymphoma. The FDA successively approved two CAR-T therapies, making CAR-T a hotspot in biomedicine , which has attracted domestic and international companies to develop their patent portfolio in the CAR-T field.

Figure 2

Before 2010, there were no patent applications in the CAR-T field in China; they did not appear until 2011. After 2015, the number of applications showed a rapidly increasing trend demonstrating that CAR-T has become a hotspot for patent applications. So far, the published CAR-T related patent applications are 946. Due to the lag in the publication of patent applications, a large number of applications in 2019 and 2020 have not yet been published. According to the growth trend shown in Figure 2, the number of applications in 2019 is estimated to exceed 300 (see Figure 2). It is expected that the number of applications in this field will continue to rise in the future.

Figure 3

Since CAR-T therapy has only recently become a hotspot in medicine, no individual large medical company has developed a strong patent portfolio. Therefore, many start-up companies, especially domestic companies and scientific research institutes, have also stepped up their research and development and applied for patents. This can also be seen from the scattered distribution of patent applicants. Figure 3 lists the distribution of major applicants with more than 9 applications. Among them, Shenzhen Binde Biotechnology Co., Ltd. has the highest number of applications, reaching 60.

Since 2015, most of the patent applications in the CAR-T field have not yet been finalized, accounting for 87.30% of total applications. Among the finalized patent applications, valid patents account for 82%, and patent applications that were rejected or deemed withdrawn account for 18%. Because of the low rate of abandonment within 5 years, the invalidity mainly resulted from rejection or withdrawal. Therefore, it is estimated that the grant rate of CAR-T field patent applications from 2015 to the present is about 82%, which is significantly higher than the average 60% in the whole biotechnology field. This may be due to the lack of similar research in this field, and so most of the relevant innovations are novel and inventive, and therefore, more likely to be granted.

3 Current situation of gene-editing related patent applications and examinations

The gene editing technology represented by CRISPR was discovered in the early 1990s. Given it has more advantages over other gene editing tools, it has quickly become the most popular gene editing method in the fields of human biology, agriculture, and microbiology. However, looking into the number of patent applications in China, we find there are about 3,600 patent applications since 2001, which is not a lot, and the number has only started to increase rapidly after 2011. The possible reason is that although gene editing technology has potentially significant medical value, the off-target problem has not been solved very effectively and there are obviously serious ethical and technical risks that people are most concerned about in clinical applications. Thus, there are still uncertainties for the foreseeable future. In 2018, hot social events related to gene editing technology drew a lot of public attention.

Figure 4

Perhaps because of the ethical and technical limitations of gene editing technology represented by CRISPR in clinical applications, companies, in particular, large multinational medical companies have not developed a patent portfolio. Applicants of patents related to this technology also show a scattered distribution. The majority of the applicants are domestic universities and research institutes. Also, the use of gene editing in the applications basically do not involve human clinical applications.

Figure 5

A large number of gene editing patent applications from 2015 to the present have not yet been finalized (83.73%). Among the finalized patent applications, the grant rate is about 69.8%, and 30.2% are rejected or deemed withdrawn. The grant rate is also higher than the overall authorization rate in the entire biotechnology field, which is about 60%.

4 Current situation of coronavirus vaccines patent applications and examinations

The overall number of patent applications in the field of coronavirus vaccines is not large (no more than 600), and the average annual number of applications basically remains in double digits, but the application number is significantly related to the outbreak and the continuation of the coronavirus epidemic. For example, the SARS epidemic in 2003 led to a significant increase in the number of patent applications from 2003 to 2004, and then with the SARS virus under control, the number of applications returned to a low level. The MERS virus outbreak in 2012 led to another period of growth in patent applications in the following years. The outbreak of the new coronavirus in 2019 has caused a significant increase in vaccine patent applications in 2020. Even though the vast majority of applications have not been published, the number of applications in 2020 has doubled compared with the number of applications in 2019. Therefore, it can be expected that the number of patent applications related to the prevention or treatment of coronavirus infection will show a significant increase in 2020 and is expected to continue to be high in the following years.

Figure 6

The distribution of applicants of coronavirus vaccines patents are also relatively scattered. Domestic applicants include scientific research institutes such as China Centers for Disease Control and Prevention, Fudan University, Second Military Medical University, and some biotechnology companies. Foreign applicants include several multinational pharmaceutical companies including Wyeth.

Figure 7

A large number of patent applications for coronavirus vaccines from 2015 to the present have not yet been finalized (87.42%). Among the finalized patent applications, the grant rate accounts for 75%, and the rejection or deemed withdrawal accounted for 25%. The grant rate is significantly higher than the overall grant rate of about 60% in the entire biological field.

Typical cases

As a typical experimental science, the predictability in the field of biotechnology is quite low. In patent examination, there are often some disputes over the predictability of technical effects. For example, the examiner may hold that the technical effects of the invention are unpredictable and the claims cannot be supported by the specification. Or, on the contrary, when there are only theoretical teachings or only general technical demand without specific technical questions, the examiner may believe that the prior art provides a motivation and the technical effect can be reasonably expected. However, this relatively subjective opinion cannot be successfully rebutted without solid evidence. The following are just a few examples to illustrate the above situation.

1 The expectations of the technical effects of biological sequences are not supported by the specification

In one case, the claim is directed to a variant of parent Bacillus alpha-amylase, wherein the parent alpha-amylase is shown to have immunological cross-reactivity with the antibody produced by -amylase having one of a sequence from SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, or SEQ ID NO.7, wherein the variant of alpha-amylase comprising sequences with R181+G182 deleted corresponding to SEQ ID NO:1, and compared to the parent -amylase, the said variant -amylase has increased thermal stability. The examiner held that the scope defined by the claims could comprise any additional mutations in addition to the double deletion of R181+G182 corresponding to SEQ ID NO:1. The biological activity of the protein depends on the spatial structure based on the amino acid sequence. Mutations of amino acid in certain sites may affect the biological activity of the protein. Therefore, if the variant contains other mutations other than RG double deletion, it may affect the thermal stability and even the biological activity of -amylase. Therefore, it is impossible for those skilled in the art to determine in advance whether those -amylase variants comprising additional mutations other than the double deletion of RG have improved thermal stability. Therefore, the examiner held that the claims could not be supported by the specification. However, the same family application of this patent was not rejected or invalidated because the open-ended claims cover sequences that are not in the examples.

2 Does general technical demand provide motivation for improvement?

A reexamined case involved a method of introduction of double-strand breaks in the target nucleic acid sequence of human cells. The examiner pointed out in the rejection that the principle of the Streptococcus pyogenes CRISPR-Cas9 system to target DNA double-strand breaks was disclosed in the prior art, and the function of Cas9 nuclease is clear. Also, gene-editing technology can allow humans to edit target genes to achieve the purpose of modifying specific DNA fragments. It is generally pursued by those skilled in the art to apply gene editing technology from in vitro, prokaryotic cells to eukaryotic cells so that this technology can be more widely used. Those skilled in the art have the motivation to use this system to introduce site-specific double-strand breaks to the target nucleic acid sequence of eukaryotic cells for a wider range of applications. Also, nuclear DNA exists in the cell nucleus and the nuclear localization sequence allows Cas9 protein to enter the nucleus to cut nuclear DNA. Therefore, it is a common technique in the field to design nuclear localization sequences to localize the target protein in nucleus. Although the prokaryotic cells and eukaryotic cells are different, those skilled in the art still have motivations to apply CRISPR-Cas9 system in eukaryotic cells and have reasonable expectation of success. The technical effect is not unexpected. On the basis that the mechanism of use of CRISPR-Cas9 system to introduce double-strand break is already known, that it is generally pursued by those skilled in the art to apply gene editing technology from in vitro, prokaryotic cells to eukaryotic cells and that this process only requires conventional techniques, the examiner held that those skilled in the art have the motivation to apply the claimed gene-editing system from prokaryotic cells to eukaryotic cells, and have a reasonable expectation of success. Although the rejection of this application was withdrawn by the PRB, the reexamination panel did not overrule the comments stated above. In the reviewing process of another patent application also directed to the CRISPR-Cas9 system, the examiner determined that one of the distinguishing features between the invention and the closest prior art is that the prokaryotic CRISPR/Cas9 system is used in eukaryotic cells. The examiner held it is not inventive on the basis that the technical effects of using CRISPR-Cas9 in Eukaryotic cells are expected based on the prokaryotic CRISPR/Cas9 system in the prior art.

These examination comments represent a trend in patent examination in the field of biotechnology, i.e., a reasonable expectation of success exists when the prior art merely offers a possibility. Thus, this underestimates the technical contribution of an invention and in a way raises the criteria of inventive step in examination.

Patent application and protection strategies and suggestions based on examination and trial practice

As mentioned above, thanks to the rapid development of biotechnology, new technologies continue to emerge, and the grant rate in the field of biotechnology, especially in emerging hotspots, is generally higher than that in other fields. However, as a typical experimental subject, patents in the field of biotechnology are faced with a situation of underestimating the innovation level of the invention during the examination process, due to the poor predictability and the strong subjectivity of the examination. Meanwhile, some factors that affect patent examination in the field of biotechnology, such as social ethics, change rapidly with the rapid development of technology and the improvement of human cognition. Such rapid change also changes the patent examination policies and standards correspondingly and frequently. For example, in order to meet the needs of technological innovation and social development, in the latest version of the Guidelines for Patent Examination, the examination criteria for embryonic stem cells based on Article 5 of the Chinese Patent Law are changed. It is important to understand and grasp such dynamic changes of the examination, which would help the applicant (or patentee) to obtain and maintain the patent rights, and protect legitimate rights and interests. Due to space limitations, the examination and trial dynamics in this technical field would be analyzed from the three articles and perspectives of experimental data and sufficient disclosure of the description, support of biological sequences, and technical suggestion in inventiveness evaluation. Corresponding strategies and suggestions are provided on such bases.

1 Experimental data and sufficient disclosure of the description

Due to the extreme complexity of life activities, it is less predictable whether or not the inventions in the field of biotechnology can be carried out successfully. They need to be confirmed by experimental data. Meanwhile, the design of an experimental scheme for obtaining the experimental data in the field of biotechnology is more complicated. It is more difficult to evaluate the experimental results (such as authenticity) only from the literal disclosures of the description. In examination practice, considering the administrative cost and operability, the examiner usually recognizes the authenticity and probative power of the experimental data based on the principle of trusting the applicant, unless the experimental data is found to have deficiencies in terms of the experiment design and/or results which are obvious enough to question the authenticity and the applicant cannot provide any reasonable explanations and clarifications. Even in patent invalidation proceedings, in order to protect the reliance interests, the burden of proof is allocated more to the invalidation petitioner who claims that the experimental data is defective. If the invalidation petitioner cannot provide sufficient evidence to deny the technical effect of the invention, and the reasons provided are not sufficient to make the collegiate panel have reasonable doubts, the collegiate panel still tends to believe in the probative power of the experimental data in the description, and to uphold the validity of the patent right. Even if there are some deficiencies in the experimental data disclosed in the description, the collegial panel would usually understand and explain in good faith, unless the deficiencies are already obvious to the extent that they cannot support each other.

However, after the former Patent Reexamination Board lost the trial of the Guipazide case, such situation is undergoing subtle changes. In this case, the court of first instance held that the experimental results on mortality and food intake provided in the description were unreasonable. Sihuans interpretations of the mortality and food intake were contrary to common sense under the premise that the original experimental report could not be provided. Accordingly, the authenticity and probative power of the experimental data disclosed in the description were not admitted, and the description was determined to be insufficiently disclosed. The original Invalidation Decision issued by the former Patent Reexamination Board was revoked. The court of second instance insisted on the Judgment of the first instance. The judgments of this case will prompt various departments of the Patent Office, including the Patent Reexamination and Invalidation Department, to further the comprehensive examination of the experimental data in the description from the formal and substantive aspects, in the subsequent substantive examination of invention patents and subsequent reexamination invalidation cases. During examination, interested parties including the invalidation petitioner will also pay attention to the experimental data disclosed in the patent documents with a critical eye, which makes it difficult for the patent applicant to sit back and relax even if it is granted. Therefore, for patent applications that have not yet been submitted, the correspondence between the items to be proved by the experimental data and the purpose of invention or the technical effect to be achieved by the invention, the logical rationality of the experimental design, and the rationality and credibility of the experimental results should be examined. Although it is not required that the description discloses the experimental examples comprehensively, the contents directly related to the inventive aspect or the technical contribution made by the invention should still be disclosed as clearly and completely as possible. Other contents not disclosed should belong to the common technical knowledge of those skilled in the art, or be facts that can be confirmed by solid evidence when being challenged. As for a patent application already submitted or granted, if it is challenged based on the experimental design being unreasonable or the experiment result unreliable, it is only possible to explain the non-necessity of the undisclosed content and the rationality of the experimental design and the results in the description by providing evidence or sufficient reasoning. If possible, the original experimental record should be submitted for consideration and support.

2 Support for biological sequence inventions

The research and development in the biotechnology field requires a large investment, has great challenges, risks, and a long return cycle. After obtaining patent rights, there are still problems like difficulties with enforcement and easy circumvention. For example, if a patent claim only protects the nucleotides, proteins, antibodies, etc. of specific sequences, it is easy to circumvent it by restructuring, selecting highly homologous sequences, etc. However, due to the large number of variable sites in biological sequences and the difficulty in predicting the effects after site modifications, a set of strict criteria on the protection scope have long been adopted for patent examination in China. This elicits frequent criticisms from the innovative entities and the patent agency industry.

Against such background, the personnel from relevant departments of the former Patent Reexamination Board conducted in-depth research on this issue. Starting from the legislative purpose, different situations were distinguished and combined with some typical cases, and more operable examination suggestions were provided on the biological sequence inventions under Article 26.4 of the Chinese Patent Law from principles and practical aspects. That is, specific examination ideas and judgment rules are provided for several common drafting manners of claims involving the biological sequences. In addition, in order to unify the examination standards, the China National Intellectual Property Administration (CNIPA) has also issued some examination standards for specific technical fields such as inventions involving antibody sequences. In recent years, judicial trials have also provided guidance on how to determine the appropriate scope of protection for biological sequence inventions in the manner of leading cases.

The above-mentioned examination ideas and rules and judicial practice guidelines for biological sequence inventions from the perspective of patent examination undoubtedly provide a good perspective and means for the application and protection of such invention patents. For example, for structural genes or their encoded protein sequences, if you want to extend the scope of protection beyond the empirical scope, you should use theoretical explanations and/or pertinent examples in the description to clarify the relationship between sequence structure and efficacy, convincing the judges that the scope of the claim can be selected or verified by those skilled in the art through experiments according to the instructions in the description or the teachings based on the common technical knowledge in the art. If you want to limit the scope of protection of the claim by homology/identity, function, and source features, it is required that the description or the prior art has clearly disclosed the corresponding relationship between the structure and function of the sequence.

3 Technical suggestion in inventiveness evaluation

At present, the CNIPA implements a comprehensive examination policy with three properties (Novelty, inventiveness, and industrial applicability) evaluation as the main line of reasoning, with the purpose of making timely and substantive responses as to whether a patent application should be granted and the scope of the right that should be granted. Under the guidance of this examination policy, inventiveness has become the most commonly used article in patent examinations. In evaluating the inventiveness, each step is carefully examined and discussed as if under a magnifying glass. For example, the relationship between the sufficient disclosure of the description and the inventiveness article, the selection of the closest prior art and its eligibility, the influence of changing the closest prior art on the inventiveness evaluation conclusion without changing the evidence combination, and the determination of the technical effect of the invention, the handling of the technical problem that the invention actually solves when it is not recognized or wrongly recognized, etc., have been studied and discussed on various occasions.

In response to a series of issues in the evaluation of inventiveness from procedure to substance, from fact finding to law application, there is a big difference in the focus and handling methods between reexamination procedure and litigation procedure. Therefore, different methods and ideas should be adopted according to the characteristics of different procedures. For example, as a relief measure after a patent application is rejected, the reexamination procedure is also a continuation of the patent administrative examination and approval procedure. Therefore, more attention is paid to the final substantive settlement of inventiveness disputes in the rejection decision. For some minor procedures or substantive deficiencies in the rejection decision, if they are not serious enough to incur an incorrect examination conclusion, the rejection decision will generally not be revoked just because of these minor procedural or physical deficiencies. Instead, the rejection decision will be upheld based on the compensation and improvement.

The litigation procedure is different. While paying attention to the substantive conclusion, the litigation procedure also pays attention to the procedural errors in the process of making the reexamination decision, and may revoke the reexamination decision on this ground. For example, many previous judgments revoked reexamination or invalidation decisions only on the grounds that the contents disclosed in the prior art, distinguishing features, and technical problems actually solved were wrongly determined, even though the final conclusion on inventiveness might be correct. Therefore, only for the consideration of the litigation strategies, it may be necessary to pay attention to the procedural or physical deficiencies in the examination process. However, it is worth noting that the Supreme Peoples Court states in its recent judgment that: when it is difficult to extract and generalize a single technical problem that is actually solved, it is necessary to return to the function and effect the technical feature play in the technical solution of the claim, and technical effect per se, instead of deliberately and subjectively extracting and generalizing a technical problem actually solved. This means that judicial practice will also pay more attention to substantive results, rather than being too entangled in the process to avoid procedural shocks. Since the Supreme Court has given such guidelines in its judgment, and the generalization of the technical problems actually solved would be subjective. Disputes often arise due to different wordings. In the subsequent examination, the Patent Reexamination and Invalidation Department would pay more attention to the technical suggestion that directly affects the inventiveness conclusion, and further downplay the identification of the technical problem that is actually solved.

Furthermore, as mentioned above, judging from the current examination practice, the examination on the relevant technical suggestion in a small number of cases has a certain bias, i.e., the abstract technical requirements are considered as the technical teaching with specific directions, thereby underestimating the technical contribution of the invention. In the field of biotechnology, after finding some important biological mechanisms, researchers usually predict their possible applications and prospects in medical or other scenarios, and immediately publicize and report them. However, the life activities are extremely complicated and unpredictable. There is still a lot of work to be done in the actual clinical application of this finding. For example, if only the concepts and principles of gene editing and cell therapy are considered, such technology would appear in the 1980s and 1990s. However, the CAR-T cell therapy technology has only recently been approved for clinical application. The gene editing has not yet been applied to the clinic. At present and in the foreseeable future, for the technologies including CAR-T technology and gene editing, we will still be committed to overcoming the deficiencies or shortcomings of its clinical application, such as finding a variety of more effective gene editing tools, overcoming off-target effects, and solving the continuous proliferation or side effects of CART cells in the body. All these efforts are inventive work that pushes a concept or idea to practical application, and their technical contributions should be recognized. Judicial practice also maintains that when confronted with the objective technical problems to be solved, the suggestion that those skilled in the art learn from the prior art should in principle be a concrete and clear technical means, rather than the abstract ideas or general research directions. Therefore, for the tendency to underestimate the technological contribution of inventions in the hearing of cases, we should try to make the judges understand and appreciate the particularity of the field through active evidence production and sufficient reasoning, and truly take in the stance of those skilled in the art. We are pleased to see that more and more patent applications directed to CAR-T and gene-editing technology getting granted. The grant rate in these emerging hotspot fields are higher than the overall grant rate in the whole field of biotechnology. This means, even though there are general demands of a certain technical solution or even the principle of how this solution will be realized has been explained, the patent application involving the technical solution is still likely to be granted as long as there are evidences showing no reasonable expectation of success exists prior to the application date.

Summary

The field of biotechnology is a rapidly developing technical field. Generally speaking, the number of patent applications in this technical field have experienced rapid and continuous growth in the past two decades. Some specific technical fields, such as CAR-T technology and CRISPR-based gene editing technology, were developed in recent years and have become a technological and social hotspot. Accordingly, the number of patent applications has increased significantly in recent years, and the number of applications in some subdivisions increases and decreases following social emergencies such as epidemics. Due to the rapid development of technology in the biological field, there are relatively few existing technologies that can affect its novelty or inventiveness. This is reflected in the higher granting rate of the patent applications than in other technical fields. Further, patent applications involving technological breakthroughs such as the CAR-T technology and CRISPR-based gene editing technology involved in this article have significantly higher granting rate than that in the biological field.

Due to complex considerations such as social ethics, as well as faster technological development and lower predictability, the field of biotechnology is more special than the field of traditional chemistry. This specialty in patent examination is mainly reflected in the more frequent changes in examination policies and examination standards. Therefore, it is necessary to have a timely and accurate understanding and grasp of the examination dynamics in this technical field. This article introduces and analyzes the current patent examination and trial dynamics from three articles or perspectives: experimental data and the sufficient disclosures of the description, support of the biological sequences by the description, and technical suggestion in inventiveness evaluation. It also provides corresponding strategies and suggestions of handling. That is, with regard to experimental data, it is recommended that for patent applications that have not yet been submitted, the drafting of the application documents should be improved from the aspects of the completeness and rationality of the experimental design and experimental results. For patents that have been submitted or granted, when they are challenged by the examiner or the public, the non-necessity of the undisclosed content and the rationality of the experimental design and results should be elaborated by evidence and sufficient reasoning. If possible, the original experimental record should be submitted for compensation and support. As to the patent protection scope involving the biological sequences, the CNIPAs current examination thinking and rules and the guidance of judicial practice should be accurately understood and grasped. As to inventiveness, appropriate differentiated response ideas and strategies should be adopted. In addition, for cases that appear in the trial in which there is a tendency to underestimate the technological contribution of inventions, we should try to make the judges understand and appreciate the specialty of the field through active evidence production and sufficient reasoning, and truly take in the stance of those skilled in the art.

Reference Documents

Original post:
Strategies and Suggestions for Patent Applications in the Hot Field of Biotechnology - Lexology

Versant debuts Ridgeline’s startup #4, armed with $30M and alternative TCR cell therapies for solid tumors – Endpoints News

For all the iterations and advances in TCR therapies for cancer, any experimental treatments involving T cell receptors share one trait: By definition, they only recognize antigens presented as peptides on the major histocompatibility complex (MHC) on cells.

Versant reckons its time to expand the arsenal. With $30 million in initial funding, its Ridgeline Discovery Engine in Switzerland has been working on a non-peptidic approach that it says has tumor-agnostic potential, especially in solid tumors. Theyve named it Matterhorn, after a Swiss mountain as they did with the three other companies that have emerged from the Basel-based incubator.

The key discoveries by founding scientists Gennaro De Libero and Lucia Mori at the University of Basel have to do with MR1, or MHC class I-related molecule 1.

When they began probing the protein more than 10 years ago, MR1 was mostly known for binding to molecules of bacterial origin and thus its role in infections. But De Libero and Mori predicted that endogenous molecules could be presented as well. And they were right. Not only did they find metabolites tied to tumor cell proliferation that are not found on healthy cells, they also stumbled upon a class of T cells that could specifically target MR1.

We published that the frequency of these cells in the blood is similar to the frequency of peptide-specific T cells, De Libero told Endpoints News. And they were overlooked.

Because MR1 is identical across humans acting as a surveillance system for aberrant metabolism, it lends itself to an off-the-shelf therapy, with no HLA matching necessary.

The idea then is to generate a library of compounds that are metabolites, that accumulate in the tumor, together with a library of predefined T cell receptors, he said. So that if your tumor expresses a compound A, you will utilize receptor A that you know is specific to that combination.

Although Matterhorns targets and receptors are new, the method of getting them into T cells isnt. Much like CAR-T and other TCR therapies, scientists will knock out endogenous TCR genes and transduce T cells with their own receptors.

Based on the preclinical data he and Mori, the CSO of Matterhorn, alongside 10 staffers have generated to date, De Libero believes that their library would ultimately consist of a relatively small number of metabolites and corresponding T cell receptors much less than 100 in total.

The research so far also indicates that while certain tumors carry rare metabolites, there are other metabolites that are present in a whole basket of different tumors and tissues. We dont want to say that we have the silver bullet against everything here, but it has a breadth that no other T cell therapy right now really has, Alex Mayweg, managing director at Versant and a board member at Matterhorn, said.

The plan now is to go through the collection of MR1 T cells and receptors theyve assembled and nominate a lead clinical candidate later this year, aiming to be ready for the clinic in early 2022. Meanwhile, the Ridgeline team will fade out as Matterhorn grows its internal payroll to 15 to 20 by the end of this year.

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Versant debuts Ridgeline's startup #4, armed with $30M and alternative TCR cell therapies for solid tumors - Endpoints News

Covid-19 roundup: CureVac beefs up its unicorn IPO dreams as billionaire owner takes this Covid-19 mRNA player on a forced march to Nasdaq; Kodak’s…

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotechs future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago bidding Merck vet Roger Pomerantz farewell from the C suite and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Covid-19 roundup: CureVac beefs up its unicorn IPO dreams as billionaire owner takes this Covid-19 mRNA player on a forced march to Nasdaq; Kodak's...

Vida Ventures co-leads Dyne’s $115M megaround for next-gen oligo therapies aimed squarely at muscles – Endpoints News

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that its got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Atlas where Dyne was incubated also returned alongside Forbion and MPM.

Stefan Vitorovic, who co-founded Vida with Arie Belldegrun and others, took the lead on this one. Dynes FORCE platform matches exactly their appetite for bold visions in the future of medicine, with the potential to deliver life-changing outcomes for patients with muscle diseases, he said.

This is how the biotech plans to do it: By linking an antibody to an oligonucleotide, Dynes therapies are engineered to hone in on muscle cells and degrade only disease-causing RNA, thereby avoiding systemic toxicity issues.

Romesh Subramanian, a co-founder of what is now Translate Bio, helped launch the operations as an entrepreneur-in-residence at Atlas. Hes since handed the CEO baton to Joshua Brumm and moved to the CSO post.

When you deliver a naked oligo, very little gets to the muscle, he told C&EN back in 2019.

That means a lack of specificity and potential safety problems for drugs like Sareptas controversial Exondys 51. While Dyne is aiming directly at that market with its Duchenne muscular dystrophy program, its initial focus is on myotonic dystrophy.

Trailing closely is a third therapy for facioscapulohumeral muscular dystrophy, followed by discovery work in the cardiac and metabolic arenas.

How would the approach compare to gene therapies, which are cropping up at Sarepta and other newer players focused on muscle diseases? We didnt get a chance to ask Dyne, which is shying away from interviews this morning perhaps a sign of upcoming plans in a booming biotech IPO market.

Under Braum, Dyne has been on a bit of a hiring spree recently, poaching Susanna High from bluebird to be COO, appointing ex-Celgene exec Daniel Wilson as VP of intellectual property, and scooping Debra Feldman from Sage Therapeutics as head of regulatory.

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Vida Ventures co-leads Dyne's $115M megaround for next-gen oligo therapies aimed squarely at muscles - Endpoints News

Edited Transcript of BLCM.OQ earnings conference call or presentation 6-Aug-20 9:00pm GMT – Yahoo Finance

Houston Aug 7, 2020 (Thomson StreetEvents) -- Edited Transcript of Bellicum Pharmaceuticals Inc earnings conference call or presentation Thursday, August 6, 2020 at 9:00:00pm GMT

Bellicum Pharmaceuticals, Inc. - CFO

Bellicum Pharmaceuticals, Inc. - President, CEO & Director

* Nicholas M. Abbott

Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology

Greetings, and welcome to the Bellicum Pharmaceuticals 2Q 2020 Financial Results and Corporate Update Conference Call. (Operator Instructions) As a reminder, this conference is being recorded. Thursday, August 6, 2020.

I would now like to turn the conference over to Stephen Jasper from Westwicke. Please go ahead.

Thank you. Good afternoon, everyone, and thank you for joining the call. With me today on the call is Rick Fair, Bellicum's President and Chief Executive Officer; and Atabak Mokari, Chief Financial Officer. Later, during the Q&A session, Aaron Foster, Head of Research, will also be available.

Earlier this afternoon, Bellicum released financial results for the second quarter and 6 months ended June 30, 2020. If you have not received this release or if you'd like to be added to the distribution list, you can do so on the Investor Relations page of the company's website.

As a reminder, today's conference call will include forward-looking statements made under the Private Securities Litigation Reform Act of 1995, including statements regarding Bellicum's research and development plans, clinical trials, plans regarding regulatory filings, review and approval of its product candidates, commercialization expectations and our financial outlook. These forward-looking statements involve a number of risks and uncertainties and reflect Bellicum's opinions only as of the date of this call. Bellicum undertakes no obligation to revise or publicly release the results of any revision to these forward-looking statements in light of new information or future events. Actual results may differ from those indicated by these forward-looking statements due to numerous factors, including those discussed in the Risk Factors section of Bellicum's Form 10-K for the year ended December 31, 2019, and 10-Q for the quarter ended June 30, 2020, filed with the Securities and Exchange Commission.

And now I will turn the call over to Rick Fair, Bellicum's President and CEO.

Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [3]

Thanks, Stephen. Good afternoon, everyone, and thanks for joining us. On our call today, I'll provide an update on our GoCAR pipeline, and Atabak will update you on our financial results. Before I talk about our individual programs, let me briefly remind you how GoCAR is differentiated from other cell therapy approaches. Our platform is unique in 2 distinct ways. First, we've engineered GoCAR to deliver more potent and durable efficacy relative to current generation cell therapies. We believe we can accomplish this primarily through our coactivation domain, MyD88, CD40 or MC. We believe MC signaling can boost effector cell proliferation and survival, enhance functional persistence by resisting exhaustion in the suppressive tumor microenvironment and stimulate the cancer patients' own immune system to attack tumors.

Second, we've engineered GoCAR for higher performance relative to current generation cell therapies, potentially offering superior control via our molecular switch technology. Other cell therapies behave unpredictably due to their autonomous activity, but GoCAR anti-tumor effects can be controlled by the scheduled intermittent administration of rimiducid. GoCAR activity can be dialed up or down by adjusting the interval between rimiducid doses or suspending further rimiducid administration. In our dual-switch product candidates, we can further improve controllability by incorporating our CaspaCIDe safety switch, which would -- can rapidly eliminate cells when triggered to manage acute toxicities if they occur.

We believe our GoCAR platform may address many of the shortcomings of current cell therapies. Our preclinical investigations have demonstrated some of these potential benefits, and we are now observing supportive evidence of these effects in the clinic. We are pursuing 2 strategic paths to establish clinical proof of concept: First, we are targeting solid tumors, where the effects of MC signaling may help overcome the challenges of the hostile tumor microenvironment, T cell exhaustion and heterogeneous antigen expression that have confounded previous CAR-T efforts. Our 2 solid tumor CAR-T -- GoCAR-T candidates, or BPX-601, targeting PSCA, and BPX-603 targeting HER2.

Our second strategy is the pursuit of an allogeneic off-the-shelf cell therapy. We believe that our GoCAR platform has the potential to drive proliferation and persistence of allogeneic immune cells and to stimulate a host immune response, both of which will be critical to delivering effective off-the-shelf therapies. We seek to demonstrate the value of our approach with our BCMA GoCAR-NK.

Let me now provide an update on each of these programs. BPX-601 targets prostate stem cell antigen or PSCA. The clinical data we have presented to date from an ongoing Phase I/II dose escalation trial in pancreatic cancer have shown encouraging safety, biologic activity, and biomarker data that supports the hypothesized benefits of the GoCAR platform in solid tumors. Specifically, we are particularly encouraged by observations of tumor infiltration, GoCAR-T mediated immunomodulation, persistence of cells for up to 9 months and changes in gene expression in the tumor microenvironment, consistent with a productive CAR-T cell immune response.

We are now enrolling Cohort 5C, our first-in-human evaluation of repeat rimiducid dosing. Our preclinical experience suggests that regular rimiducid dosing can reactivate and expand GoCAR-T cells in the presence of tumor antigen over time, without creating T cell exhaustion and thus, maximize the clinical efficacy potential. We plan to present interim results for this cohort at a medical meeting by the end of this year.

Like many others, we have experienced the COVID-19 related impact on screening and enrollment, which may impact the number of patients and duration of follow-up that we will present. In addition, primarily due to COVID-19 restrictions at our study sites, we have been unable to date to collect post-treatment biopsies in Cohort 5C, limiting to some degree what we can assess in these patients. We will continue to work with our investigators to overcome these COVID-19 obstacles to the extent possible, and are in the process of adding a few more sites to the study to increase prescreening activity.

Looking ahead, we have submitted a protocol amendment to the FDA with several modifications to the study. Upon FDA and IRB clearance of this amendment, we plan to expand eligibility to third-line pancreatic cancer patients, which we believe will enable more prescreening. Second, informed by the risk-benefit profile we've observed to date, we will extend dose escalation to 10 million cells per kilogram. Lastly, we will add a cohort of patients with hormone refractory, metastatic castration-resistant prostate cancer. Assuming prompt FDA clearance of this amendment, we expect to begin enrollment under this amended protocol later this year. Based on the data we've seen so far and the proposed study amendments, we remain optimistic about BPX-601, both as a product candidate and as proof-of-concept for our GoCAR platform.

Now let me update you on BPX-603. This program is Bellicum's first dual-switch product candidate, which has been designed to target solid tumors that express HER2. Academic CAR-T trials targeting HER2 have demonstrated clinical activity and reasonable safety. We believe that our dual switch technology in BPX-603 may be uniquely suited to improve upon these earlier efforts by driving greater efficacy through MC signaling and providing an extra layer of safety via our switch platform.

The FDA recently cleared our IND for BPX-603, and we are currently in study start-up to initiate a Phase I/II clinical trial later this year. The trial is a traditional 3 plus 3 dose escalation followed by Phase II expansions in multiple HER2-positive cancers. Dose escalation will begin at 100,000 cells per kilogram in a basket of HER2-positive solid tumors, and patients will be sequentially enrolled throughout dose escalation. Patients will receive standard Flu/Cy conditioning followed by BPX-603 cells. The first patient in each dose cohort will be followed without subsequent treatment, while the remaining patients in each cohort will receive weekly rimiducid to either dose-limiting toxicity or disease progression. We are excited to get this study underway, and we'll keep you posted on our progress.

Now let's move to our BCMA GoCAR-NK program. CAR-NK cells represent an intriguing next wave in the evolution of cell therapy, so we are excited about the potential for our first off-the-shelf GoCAR-NK candidate. NK cells may be particularly well suited for allogeneic cell therapy since they have innate cytotoxicity with low propensity for causing graft-versus-host disease.

We presented encouraging preclinical data from our NK discovery program at the 2019 SITC meeting and published a paper on this work, Blood Advances, this year in May. The data showed that our GoCAR platform synergizes with secreted IL-15 to enhance NK cell proliferation, survival and cytotoxic function. In addition, GoCAR-NK cells expressing our MC coactivation domain and IL-15 resulted in superior in vivo efficacy in multiple preclinical tumor models. Based on these initial investigations, we believe that GoCAR-NK cells have the potential to be a best-in-class off-the-shelf cell therapy. We selected BCMA as the target for our initial program since it is, well validated from autologous CAR-T studies, and we expect cell therapy to play a major role in multiple myeloma treatment.

The next step for the field is to deliver similar clinical benefit with an off-the-shelf therapy, which may provide faster and more certain time to treatment, greater scalability, convenience and a lower cost to manufacture. Based on our preclinical findings, we believe that GoCAR-NK may deliver more durable efficacy than other off-the-shelf cell therapy strategies. We will seek to demonstrate this in our development program. Our preclinical development is ongoing, and we expect to present additional data for this program by the end of 2020.

That concludes the summary of our programs. So let me now turn the call over to Atabak for a review of our financial results.

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Atabak Mokari, Bellicum Pharmaceuticals, Inc. - CFO [4]

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Thank you, Rick. R&D expenses were $11.8 million for the second quarter of 2020 compared to $20 million for the second quarter of 2019. The reduction in expenses in the second quarter of 2020 was primarily due to reduced expenses related to reduced RIVO-CEL-related activities, reduced expenses resulting from the April 2020 manufacturing facility sale and the reduction in force that was implemented during the second half of 2019. These reduced expenses were partially offset by increased expenses related to our GoCar-T and GoCAR-NK programs.

General and administrative expenses were $3.8 million for the second quarter of 2020 compared to $7.5 million during the comparable period in 2019. The lower expenses in the second quarter of 2020 was primarily due to the reduction in RIVO-CEL-related commercialization activities and the effect of the reduction in force that reduced employee-related charges.

Bellicum reported a net loss of $43.2 million for the second quarter of 2020 compared to a net loss of $26.9 million for the comparable period in 2019. The second quarter 2020 results included a noncash loss of $30.7 million related to the change in fair value of warrant liability and net gain on dispositions of $3.8 million due to the manufacturing facility sale.

Turning to our balance sheet. As of June 30, 2020, cash, cash equivalents and restricted cash totaled $68 million. In the second quarter, we had a cash loss from operations of approximately $14.2 million, which was a decrease from prior quarters given the steps we have taken to streamline the organization.

In April, Bellicum closed a transaction in which the MD Anderson Cancer Center acquired our manufacturing facility in Houston for $15 million. Concurrent with the transaction, Bellicum repaid $7 million of its Oxford Finance debt obligation.

Based on current operating plans, Bellicum expects cash utilization of $55 million to $65 million for the full year 2020 compared to cash loss from operations of approximately $30.5 million for the 6 months ended June 30, 2020. We believe that the current cash resources will be sufficient to meet operating requirements into the second half of 2021.

And now I'll hand the call back over to Rick.

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [5]

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Thanks, Atabak. Reviewing our accomplishments so far in 2020, I'm pleased by the advancement of our GoCAR pipeline across our 3 programs. I'm particularly enthusiastic as we anticipate an increasing number of potential data milestones. Over the next 24 months, for BPX-601, we expect to present 2 updates in pancreatic cancer and our first data in prostate cancer. For BPX-603, we expect steady start in our first patient from dose escalation. And for our GoCAR-NK program, we expect multiple preclinical presentations and IND submission.

I remain excited about Bellicum's future, the potential of our GoCAR pipeline and look forward to updating you on our future progress, including our first-in-human data with repeat rimiducid dosing and preclinical data on our GoCAR-NK program later this year.

I'll now open the call to questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from the line of Jim Birchenough with Wells Fargo Securities.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [2]

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It's Nick on for Jim. And keeping us on the toes there with a new way to register and address all of your question. So the first thing, Rick, on 601. So has there been any readthrough from emerging repeat dose rimiducid data that's sort of led to this, I think, what we'd interpret as a renewed interest in expanding the 601 program?

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [3]

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No, I think the expansion in the prostate, which is probably what you're referring to, Nick, is -- been a long-standing interest of ours. And I think we've now -- we're approaching the end of the dose escalation that we initiated in pancreatic cancer and now's the time to explore an expansion mode, a different tumor type. I think we all acknowledge that pancreatic cancer is a very challenging tumor. And we certainly don't want to miss a signal by not looking a little more broadly. So I think this is really just fulfillment of the previously articulated plan.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [4]

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Okay. And then, in terms of the patients that you'll be enrolling with prostate cancer, do they have to fail the specific number of lines of treatment? And then, just from a perspective of this is a very bone-centric cancer, do you have preclinical data that supports that 601 is able to penetrate bone mets?

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [5]

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Yes. On your first question, eligibility inclusion criteria, patients have to have received an anti-androgen therapy and either received or are ineligible for a taxane. And then for the subsets of patients that qualify, either MSI-high for anti-PD-1 or BRCA mutant for PARP inhibitor have to have received those therapies as well. So it's a later line patient population.

As far as bone mets, I don't think we have any specific preclinical data for BPX-601, but we will certainly be looking at the translational data as we embark and treat the patients in the study.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [6]

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And then just on 603, you gave us some outlines on -- of the trial design, so 3 plus 3, those patients. So is that the first patient at every dose level would not receive rimiducid?

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [7]

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Yes, that's correct. The -- so it's a traditional 3 plus 3 design with some modifications, and that's certainly one of them. So you would expect in each cohort and dose level in each of the study, the first patient would receive cells only, and the second 2 patients in the absence of a dose-limiting toxicity would receive cells plus weekly rimiducid.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [8]

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And so presumably that first patient then will stay in the hospital, be intensively monitored. Do you have -- I mean, what -- can you discuss what the triggers are for administering the rapalog to activate the kill switch?

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [9]

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I think in summary, depending on the toxicity, it's essentially failure of standard of care. So these patients, as you say, will be admitted and will be monitored carefully. The on-target, off tumor effects that you'd be most interested in with this antigen, of course, are cardiopulmonary. So certainly, we'll be active monitoring. And if adverse events occur, they'll be treated with standard of care for whatever the adverse event. And then if standard of care fails, then they'll receive tensile and the small molecule activator of the safety switch in this construct.

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Operator [10]

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Our next question comes from the line of Kit Ma with Jefferies.

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Wai Kit Ma, Jefferies LLC, Research Division - Equity Associate [11]

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This is Kit. I'm on for Biren. I'm wondering what type of response can we expect with BPX-601 in the current trial. What will be the bar to move this forward into Phase II trial?

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Richard A. Fair, Bellicum Pharmaceuticals, Inc. - President, CEO & Director [12]

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Sure. Thanks, Kit. So it depends on the tumor type, of course. I think what we've said about pancreatic cancer is that you'd need to see something like a 15% response rate with a 6-month duration of response to be meaningful activity in the setting and be worth expansion in prostate cancer, probably a bit higher on the response rate, something more like a 30% to 35% response rate with similar durability to be a meaningful candidate to advance. So those are the thresholds that we're looking at.

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Operator [13]

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(Operator Instructions) Our next question comes from the line of Wangzhi Li with Landenburg.

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Wangzhi Li, Ladenburg Thalmann & Co. Inc., Research Division - MD of Equity Research of Biotechnology [14]

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Edited Transcript of BLCM.OQ earnings conference call or presentation 6-Aug-20 9:00pm GMT - Yahoo Finance