Three UCLA scientists receive grants totaling more than $18 million – UCLA Newsroom

Three researchers at theEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLAhave received awards totaling more than $18 million from the California Institute for Regenerative Medicine, the states stem cell agency.

The recipients are Dr. Sophie Deng, professor of ophthalmology at the UCLA Stein Eye Institute;Yvonne Chen, a UCLA associate professor of microbiology, immunology and molecular genetics; and Dr. Caroline Kuo, a UCLA assistant clinical professor of pediatrics. The awards were announced at a CIRM meeting today.

Dengs four-year, $10.3 million award will fund a clinical trial for a blinding eye condition called limbal stem cell deficiency. Limbal stem cells are specialized stem cells in eye tissue that help maintain the health of the cornea. Because of genetic defects or injuries caused by infections, burns, surgeries or other factors, some people do not have enough limbal stem cells, which results in pain, corneal scarring and blindness.

The approach she is testing involves extracting a small number of limbal stem cells from a persons eye, multiplying them in a lab, and then transplanting them back into the eye, where they could regenerate the cornea and restore vision. The research will be conducted in collaboration with theUCLAUCI Alpha Stem Cell Clinic, a partnership between UCLA and UC Irvine.

The grants awarded to Chen and Kuo are for projects that are heading toward the FDAs investigational new drug application process, which is required by the agency before a phase 1 clinical trial the stage of testing that focuses on a treatments safety.

Chens two-year, $3.2 million award will fund efforts to create a more effectiveCAR T cell therapyfor multiple myeloma, a blood cancer that affects white blood cells. The research will evaluate a specialized form of CAR T therapy that simultaneously targets two markers, BCMA and CS1, commonly found on multiple myeloma cells. CAR T therapies that target BCMA alone have been effective in clinical trials, but the presence of BCMA on multiple myeloma cells is not uniform.

Previous research has shown that the marker CS1 is present in around 90% of multiple myeloma cells. A CAR T therapy that targets both markers could potentially help more patients and reduce the likelihood of a cancer relapse.

Kuos 2 1/2-year, $4.9 million award, will support the development of a stem cell gene therapy for a deadly immunodeficiency called X-linked hyper IgM syndrome, or XHIM.

The syndrome, which is caused by a mutation in the CD40LG gene, results in invasive infections of the liver, gastrointestinal tract and lungs. Currently, the only potential cure is a bone marrow transplant from a matched donor, which carries life-threatening risks and is often less effective for XHIM patients than patients with other forms of immune deficiency. Even with current treatments, only 30% of people with the syndrome live to age 30.

Kuo will evaluate a stem cell gene therapy that corrects the genetic mutation that causes XHIM. After removing blood-forming stem cells from a person with the syndrome, the therapy would use a genetic engineering technique called CRISPR to insert a correct copy of the affected gene into the DNA of the stem cells. The corrected blood-forming stem cells would be infused back into the patient, where they could regenerate a healthy immune system.

She will collaborate with Dr. Donald Kohn, a UCLA distinguished professor of microbiology, immunology and molecular genetics who has successfully treated two other immune deficiencies bubble baby disease and X-linked chronic granulomatous disease with a similar therapy.

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Three UCLA scientists receive grants totaling more than $18 million - UCLA Newsroom

Can This Cell Therapy Help Fight the NASH… – Labiotech.eu

Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD) and is characterized by a fatty liver, inflammation, and liver cell damage. If left untreated, NASH can further develop into liver fibrosis, the formation of scar tissue in the liver, and liver cirrhosis. To date, a patients only option at the final stage of liver disease is a liver transplant. There is no alternative available yet.

This year alone has already seen a number of disappointments within the NASH clinical trial landscape. In April, Gilead announced that its anti-fibrosis compound selonsertib failed to reach the endpoint in phase III. In June, Conatus and Novartis NASH cirrhosis treatment emricasan also missed its primary endpoint in a phase IIb trial. And although Intercepts Ocaliva showed an effect on fibrosis in phase III, the results were overshadowed by strong side effects.

The therapy landscape for NASH is currently dominated by small molecules that address defined targets. Many of the currently ongoing trials are focusing on the earlier stages of NASH, covering the fibrotic stages F1 and F2. The later stages of NASH, F3 and F4, on the other hand, are receiving attention at the clinical stage but are difficult to treat.

If you look at the number of therapies in development for cirrhotic NASH F4 and indications further down the disease progression path, you will find a blue ocean, says Henrik Luessen, CBO at Promethera. There is not much competition to be found in that space. NASH is a spectrum disease in which many factors play a role, including inflammation, immune activation, stellate cell activation, lipid metabolism, and fibrosis. Most molecules can only target one of these factors and the action is therefore very limited. In later stages, where many more factors are involved, there is a need for an approach that addresses more than one target. That is the key challenge in NASH.

Promethera has taken a leap into the blue ocean and has developed a cell therapy in which liver-derived cells can address several factors of the disease. These cells have a potent paracrine effect and are able to respond to the cause of the disease by secreting or expressing various molecules, including hepatic growth factor (HGF), indoleamine 2,3-dioxygenase (IDO), and prostaglandin E2 (PGE2), to reduce inflammation, inhibit stellate cell activation, and to further interrupt the fibrotic or cirrhotic process and restore liver function.

Based on the behavior of our cells observed over more than six years of intense clinical research following the inception of Promethera, we decided to focus on end-stage NASH and acute-on-chronic liver failure (ACLF), the end-stages of the disease where patients are suffering from at least one organ failure and have a very low prognosis to survive the next three months, Luessen explains. When we found promising signs of efficacy and safety in ACLF we decided to move further into the NASH field and focus on the late stages of the disease where there is a strong unmet medical need. In both cases, we are positioning our cells as an alternative to liver transplantation.

The data of the completed HEP101 study in ACLF patients will be published at the upcoming American Association for the Study of Liver Diseases (AASLD) meeting in Boston on 10th November 2019, for the first time.

Moreover, in May 2019, Promethera started the PANASH study, which is evaluating the safety of HepaStem in NASH F3 and F4 patients at different dosages. Efficacy markers will also be investigated as a study outcome.

Prometheras pipeline is comprised of two allogeneic cell therapies and one antibody. Designed to target the tumor necrosis factor receptor 1 (TNF-R1), the companys antibody Atrosimab is currently in preclinical development. TNF is known to interact with receptors one (R1) and two (R2). While R1 is responsible for triggering inflammatory responses and apoptosis, R2 is actually a type of regenerative receptor.

Classical TNF inhibitors inhibit all systemic TNF, including all interactions with R2, Luessen says. Atrosimab only inhibits R1, which allows the regenerative properties of R2 to be maintained. It can also be potentially used in combination with our HepaStem technology.

HepaStem, currently in phase II, is a cell therapy that addresses different components of the NASH disease progression. Consisting of liver-derived mesenchymal stem cells (MSC), HepaStem is administered intravenously without the need for immunosuppressants and enters the liver via the bloodstream, where it then targets multiple changed pathways. HepaStem can reduce tissue fibrosis and promote the restoration of liver function by lowering inflammation, deactivating stellate cells, and reducing fibrosis.

Prometheras second cell therapy, H2Stem, is currently at a preclinical stage. H2Stem are liver-derived progenitor cells from the hepatobiliary tract that can express various markers, can differentiate into hepatocyte-like cells in vitro and have been observed to home and repopulate the liver of humanized mice. H2Stem has shown good signs of engraftment in mice, which allows us to assume that it might have strong regenerative or repair properties, but we are still collecting evidence, says Luessen.

Prometheras allogeneic cell line is unique in that it also has the potential for liver homing, meaning the cells have a liver imprint and remain in the liver where they can fight the cause of the disease. Moreover, the cells do not provoke immunogenic responses, which enables the intravenous injection of the therapy without needing immune suppression. Even a second injection, triggers no acute immunogenicity or toxicity.

Our product has undergone the chemistry, manufacturing, and controls (CMC) part of development, Luessen explains. This means that we have a very scalable product. We are now moving to bioreactors, which will allow us to treat thousands of patients with only one liver. We are confident that we can meet global demand with our new in-house process, in particular when we move to our state-of-the-art facilities in Gosselies, Belgium, in 2020. At the moment, the only option for end-stage liver disease patients is a liver transplant, so with one liver we could avoid a very high number of liver transplants, at least exceeding the currently recorded global numbers of transplants. Thats what makes our technology unique and very promising.

Many companies are now becoming increasingly aware that addressing only one target in early-stage NASH does not add many benefits to patients, Luessen says. In fact, patients often have to take several medications continuously, which can come with unpleasant side effects. Furthermore, early-stage NASH patients can greatly benefit from lifestyle changes, including dietary measures and physical exercise.

In the early stages of NASH, during F1 and F2, many patients are not aware of their disease because they do not show any symptoms. Once the disease is felt, patients are often already in the later stages, F3 and F4, and here, the medicinal landscape becomes very poor, Luessen explains. Looking at the future, I think this will be recognized and there will be a greater focus on the fibrotic and cirrhotic stages of NASH. We can already see different pharma companies, who are usually competitors, working together. They are combining their compounds to have a more efficient treatment. This will be the only way to address the disease outside of cell therapy.

Do you want to discover more about how Prometheras cell therapy could revolutionize NASH treatments? Check out Prometheras website for more information or get in touch with their experienced team!

Images via Promethera and Shutterstock.com

Author: Larissa Warneck, Science Journalist, Labiotech.eu

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Can This Cell Therapy Help Fight the NASH... - Labiotech.eu

Interview With Chaim Lebovits, CEO Of Brainstorm Cell Therapeutics – Seeking Alpha

This level of disease stabilization has not been observed to this date in approved or investigational ALS therapies.

- Mr. Chaim Lebovits, CEO, Brainstorm Cell Therapeutics

In May of this year, I published an article on Brainstorm Cell Therapeutics (BCLI). This small company is developing a mesenchymal stem cell product called NurOwn, which is in late phase 3 trials targeting amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. My article was bearish, deploring not only the company's cash position but also phase 2 trial data. The article can be read here.

That article received a lot of critical comments from the ALS community. That made me realize that a fair overview of the issues could be best addressed by going through the comments, as well as my own coverage, and by asking BCLI management, specifically its CEO, Chaim Lebovits, to clarify some of these issues. So, that's what I did. I emailed a set of 11 questions to Mr. Lebovits, and he was kind enough to respond to them in great detail. The entire interview, sans any edits, is available to Total Pharma Tracker members.

Mr. Lebovits has been with BCLI for well over 12 years, joining in 2007 as president and also becoming the CEO in 2015. He has helped develop NurOwn through its preclinical stage to its current stage and is, therefore, just the right person to talk to if we want to understand NurOwn and BCLI.

I began by asking him to locate NurOwn in the ALS therapy space and where it stands with respect to competitors. What's its mechanism of action, and how does that MOA distinguish it from the competition?

Mr. Lebovits said that there are "currently 4 products active in phase 3 ALS clinical trials (Brainstorm (NurOwn, autologous MSC-NTF cells secreting neurotrophic factors), Orion (levosimendan, muscle troponin calcium sensitizer), Orphazyme (arimochlomol, heat shock protein enhancer), and Biogen (SOD1, antisense oligonucleotide)." Top-line data from these ALS phase 3 trials is expected in 2020 (Q4 2020 for Brainstorm) and Orion, 2021 (Orphazyme), and 2022 (Biogen). He discussed a number of earlier-stage compounds as well as various stem cell therapies. He said that what distinguishes NurOwn among ALS therapies is that it "confers both neuroprotection and immunomodulation by delivering neuronal survival factors and immune regulatory molecules, including microRNA directly to the CNS compartment at or near the site of disease, and therefore directly addresses two important ALS disease mechanisms."

Among stem cell therapies, Mr. Lebovits said that NurOwn distinguishes itself by being autologous and because it can produce high levels of neurotrophic factors. Moreover, unlike most stem cell competitors, it's delivered directly into the spinal fluid through bimonthly lumbar punctures, unlike others that need an invasive surgical procedure "that carries considerable morbidity."

This feature it shares with a competing product from Corestem. However, it's differentiated from Corestem because "NurOwn is more convenient than the Corestem product as a single bone marrow cell harvest due to validated cryopreservation, whereas the Corestem product requires repeat bone-marrow aspiration for each treatment."

My next question was a technical question about pharmacoresistance. I wanted to know how NurOwn is managing to cross the blood-spinal cord barrier despite the strong pharmacoresistance (body's resistance to drugs) seen in ALS, specifically for disease-modifying neurotrophic factors. What was it about NurOwn's delivery mechanism that the company thinks is overcoming this natural resistance. So I asked: "Talking about MOA, pharmacoresistance is a disease driving mechanism in ALS. Can you discuss NurOwn's delivery mechanism vis-a-vis the inability of neurotrophic factors to effectively cross the blood-brain barrier, or, specifically, the blood-spinal cord barrier (BSCB)? Please correlate that discussion regarding the observed increase in CSF NTFs post-treatment as seen in the phase 2 trial."

Mr. Lebovits explained this with great clarity - for his entire response, take a look at the complete interview. Broadly, what he said was that NurOwn, being delivered through lumbar puncture directly into the spinal fluid, has an advantage. Moreover, the cells secrete neuronal survival factors as well as molecules that regulate the immune system, so that they are able to survive and overcome the pharmacoresistance. Systemically administered NTFs are unable to do that.

As he said, "In the phase 2 trial, CSF biomarkers obtained just prior to treatment and two weeks afterward demonstrated that MSC-NTF cell-secreted neurotrophic factors were significantly increased post-treatment and correlated with the reduction in inflammatory biomarkers, consistent with the proposed mechanism of action."

My third and fourth questions related to aspects of the phase 2 study. One, comparison of safety and efficacy data with competitors, and two, the relevance of the reported caspase-3 reduction of 60% in responders versus 30% in non-responders.

Mr. Lebovits said that although the phase 2 study was not powered for efficacy, it exhibited a "level of disease stabilization (that) has not been observed to this date in approved or investigational ALS therapies." About the ongoing phase 3 study, he said the following:

Those who read my original article will recall I was particularly puzzled by the increased occurrence of serious adverse events in active-treatment groups than in placebo groups. 8/36 or 22.2% patients in the treatment arm had an SAE compared to only one out of 12 placebo patients, or 8.3%. Most SAEs were related to the progression of the underlying ALS, most commonly dysphagia. No SAEs were related to study treatment. So I asked Mr. Lebovits how this data could be interpreted in the most positive way.

According to him, this decline was not an effect of treatment itself and simply indicated the need for repeat dosing in this patient group. His exact response was as follows:

The MSC-NTF treated group had a slightly more rapid rate of decline compared to the placebo group in the three-month run-in period and most ALS disease progression in the treated group was seen toward the end of the clinical trial, long after a single transplantation. In fact, the bulbar subscale, that includes assessment of swallowing, was the subscale most improved after MSC-NTF treatment in rapid progressors, suggesting that the late decline in motor function was not an adverse effect of treatment per se. Hence the need for repeated dosing.

Last week, the DSMB recommended continuation of the phase 3 trial without any modification. This was major good news, so we asked him about this. Mr. Lebovits said that this was a second interim safety review, and there were no significant safety concerns. Therefore, the DSMB recommended no modification in protocol and no other interim analysis is planned. Phase 3 data will be available by mid-2020 according to this interviewer's reading of the press release.

Now we moved on to another critical aspect of our analysis - funds, or rather, the lack of it. Since this is an important issue, here's the exact exchange we had.

Dr. Ashok Dutta: How does the company plan to fund its operations through the next couple years until the lead development candidate is approved and commercialized? Given the weak financial position, does Brainstorm see the possibility for ATM operations, or thinks about selling rights in regions like China, Japan or Europe to increase the financial condition?

CEO Chaim Lebovits: As you are aware we do receive proceeds from the hospital exemption pathway and also receive grant funding from CIRM and IIA. These avenues have allowed to fund and continue with our trials over the years with non-dilutive financing. From a business standpoint as our ALS phase 3 trial is now fully enrolled, the management team continues to hold high level conversation with some of the leading global pharmaceutical and biotechnology companies. We are actively engaged in strategic partnering and collaboration discussions and although we cannot disclose the details of our conversations due to NDAs we signed with them... we are exploring several opportunities with key interested parties to advance the opportunities for NurOwn development and commercialization. As you have rightly pointed out, we have a $20mm ATM facility in place with Raymond James. We may activate the ATM as required and raise up to $20mm by selling our stock "at the market" only if the prices are attractive to us. So far as of end of Q3'19, we have not activated the ATM. If the need arises and the prices are attractive to us, we may employ this tool to raise capital.

This is reassuring that the company intends to focus on non-dilutive financing. The ATM facility, coupled with the grants, should ideally see them through the approval phase. We still wonder how they will manage marketing and sales. Perhaps those commercialization NDAs they have signed will help.

Next, we discussed market potential and a question about a recent patent grant. The CEO's detailed responses can be found in the complete interview material.

The strong involvement of the ALS community impressed us previously, so we now asked the CEO about the recent roundtable convention they had with ALS advocacy groups. Since this will be important for the ALS community as a whole, here's Mr. Lebovits' entire response on the question:

Finally, we asked him what we ask everyone: Give us three simple and straightforward reasons why investors would be interested. Here's what he said:

Thanks to the ALS community for inspiring us to conduct this interview, and to Mr. Chaim Lebovits, CEO of Brainstorm Cell Therapeutics, for answering our questions.

Thanks for reading. At the Total Pharma Tracker, we interview management of important small biotech doing disruptive work in healthcare. Our members are given exclusive access to these interviews, which helps them with additional primary resource in doing DD on their investments. Sometimes, extracts from these interviews may be published for everyone; but TPT members always get the exclusive view.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: General Disclaimer - This is to confirm that Avisol Capital Partners has neither requested, nor been offered, any monetary compensation for conducting this interview, by any party other than Seeking Alpha.

Also to be noted, this was an emailed questionnaire, and certain editorial material is present in this version, which may or may not reflect BCLI or its CEO's position on the issues discussed.

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Interview With Chaim Lebovits, CEO Of Brainstorm Cell Therapeutics - Seeking Alpha

Galera Therapeutics And Amgen In Severe Oral Mucositis – Seeking Alpha

Therapeutic Differentiation

Galera Therapeutics (GRTX) is a privately-held company that recently filed for an IPO. Its clinical focus is on developing Phase 3 lead investigative drug candidate, avasopasem manganese (formerly GC4419), to treat severe oral mucositis (SOM) associated with head and neck cancer (HNC) radiotherapy.

Oral mucositis (OM) occurs when radiotherapy induces the production of superoxide that attacks and breaks down the epithelial cells lining the mouth. The severity of OM is commonly measured using the WHO scale consisting of five Grades: Grade 0 through Grade 4 with SOM is commonly defined as Grade 3 or Grade 4 OM (discussed later).

Therapeutically, the annual addressable market for oral mucositis in G8 countries was estimated to be $638.8M in 2016 with a subsequent global annual projection of $2.6B in future years. In the US, ~500,000 individuals are diagnosed with OM annually and the prevalence is expected to rise in parallel with an increasing incidence of HNC projected at 65,000 every year.

SOM is a serious non-hematological complication of cancer associated with both chemotherapy and radiotherapy treatments. When caused by chemotherapy, mucositis is usually due to the low white blood cell count. In contrast, radiotherapy mediated mucositis is usually due to necrotic and inflammatory effects of radiation energy on oral mucosa.

In Q1/2018, Superoxide dismutase (SOD) mimetic, avasopasem manganese (formerly GC4419), received FDA Breakthrough Therapy Designation for the reduction of the duration, incidence, and severity of SOM induced by radiotherapy. GRTX thesis is that avasopasem manganese is therapeutically differentiated from the only FDA approved therapeutic for SOM, Kepivance, because it:

has the potential to address and mitigate the root cause of radiotherapy-induced mucositis, including OM and esophagitis. By removing superoxide, GC4419 is designed to reduce the damage radiotherapy causes to the patient's normal tissue, and thereby reduce the incidence and severity of mucositis.

In 2004, Kepivance (formerly palifermin), a recombinant human keratinocyte growth factor developed by Amgen (AMGN), was approved to reduce the incidence and duration of SOM in patients with certain types of blood cancer (i.e. hematologic malignancy) who are being treated with high-dose chemotherapy and radiation therapy followed by a stem cell transplant. It protects the epithelial cells that line the mouth and throat from the damage caused by chemotherapy and radiation and by stimulating the growth and development of new epithelial cells to build up the mucosal barrier.

The safety and efficacy of Kepivance have not been established in patients with non-hematologic malignancies and this represents an important clinical differentiation from GC4419. Since its approval in 2004, Amgen has advanced the clinical development of Kepivance (palifermin) for other hematological indications as reflected in ongoing clinical trials.

Specifically, it is being studied in the prevention and treatment of common side effects in other types of cancer. If clinically successful, this would expand the addressable market for Kepivance.

At the end of Q3/2019, AMGN reported cash and investments of $20.9B and free cash flow of $3.2B. Total revenues in Q3/2019 decreased by 3% to $5.7B relative to Q3/2018. Analysts recommend a buy with a 12-month price target of $220.79. Institutional ownership stands at 78.91% based on 13F filings and accounting for 1,969 Institutional holders with 468,873,044 total shares.

Superoxide dismutases (SODs) are protein enzymes that provide antioxidant defense against the pathophysiological effects of reactive oxygen species (ROS)/oxidative stress in diverse disease states. These protein enzymes convert superoxide to molecular oxygen and hydrogen peroxide (Fig. 1). Hydrogen peroxide is much less toxic than superoxide to normal tissue but more toxic to cancer cells. Radiotherapy induces a large burst of superoxide in the irradiated tissues, which can overwhelm these SODs, damaging normal cells.

Figure 1: (A) The generally accepted catalytic mechanism for dismutation of O2 - by superoxide dismutase (SOD). (B) Subunit structure of bovine Cu, Zn-SOD (Protein Data Bank Entry, 2 SOD).

Elevated ROS/Oxidative stress has been implicated in cancer progression. Furthermore, targeting antioxidant enzymes is increasingly perceived as an important radiosensitizing strategy to reduce the resistance of cancer cells to radiotherapy. Pharmacologically, GRTX describes GC4419 as selective, stable in vivo and does not react with other oxygen species, and its low molecular weight contributes to its ability to access a cell's cytosol and mitochondria. Notably, GRTX notes that:

The ability to develop a low-molecular-weight synthetic enzyme that harnesses the power of dismutase mimetics to function as a radiation response modifier, with efficient chemical synthesis and stability, offers a new paradigm for drug design.

By rapidly converting superoxide to oxygen and hydrogen peroxide, GC4419 works to reduce elevated levels of superoxide caused by radiation, which can damage noncancerous tissues and lead to serious side effects, including oral mucositis.

The WHO scale description of Mucositis manifestation is as erythema (Grade 1), edema and/or ulceration but patients can swallow solid food (Grade 2) to ulceration with extensive erythema and patients cannot swallow solid food (Grade 3) and large and painful ulcers that worsen patient quality of life and limit basic oral functions such as speech, the swallowing of solid or liquid is not possible (Grade 4).

The data from a Phase 2b study of GC4419 in SOM associated with HNC demonstrated a reduction in:

the duration of SOM from 19 days to 1.5 days (92 percent), the incidence of SOM through completion of radiation by 34 percent and the severity of patients' OM by 47 percent, while demonstrating acceptable safety when added to a standard radiotherapy regimen.

In addition, in multiple preclinical studies, GC4419 demonstrated an increased tumor response to radiation therapy while preventing toxicity in normal tissue.

The Phase 3 confirmatory, randomized, placebo-controlled registrational trial of a 90 mg dose of GC4419 in patients with locally advanced head and neck cancer receiving radiotherapy was initiated in Q4/2018 with topline data anticipated in the first half of 2021.

At the end of Q2/2019, GRTX reported cash and cash equivalents and investments of $81.2M (S-1/A prospectus). Investors include Novo Ventures, Novartis Venture Fund and many more. GC4419 has multiple shots on goal with its Phase 1/2 clinical evaluation for pancreatic cancer (Fig. 2).

Fig. 2: Clinical Development of GC4711.

GRTX retains worldwide rights to GC4419. The IPO of 5M common shares has been set at $14 - 16.

In Q4/2019, GRTX reported on the long-term clinical effects of GC4419 in a two-year tumor outcome assessment:

As part of its Phase 2b clinical trial of GC4419 in patients with locally advanced head and neck cancer, Galera assessed tumor outcomes of the patients over a two-year period following radiotherapy. Patients in the trial received seven weeks of radiation therapy plus cisplatin, and were treated with either 30 mg or 90 mg of GC4419 or placebo by infusion on the days they received their radiation treatment. At both the one-year interim assessment and final two-year mark, tumor outcomes were maintained across all four measures - overall survival, progression-free survival, locoregional control and metastasis-free survival - in both GC4419 dose groups (30 mg and 90 mg) compared to placebo.

We are pleased with these data, which demonstrated GC4419, when added to a standard radiotherapy regimen, maintained the efficacy of treatment for head and neck cancer and reduced debilitating radiation-induced oral mucositis," said Mel Sorensen, M.D., President and CEO of Galera Therapeutics. "GC4419 achieved meaningful reductions in the duration, incidence and severity of SOM in the completed Phase 2b trial. These two-year tumor data further reinforce the potential of GC4419 to be a promising treatment to reduce radiation toxicities and complement standard radiotherapy regimens in head and neck cancer.

Thanks for reading. While I occasionally cover companies like this, my focus remainsinvestment opportunities in liver therapeutics, specifically, NASH and Cholestatic liver diseases exclusiveto members of my private investing community, Liver Therapy Forum,a teaching marketplace.

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Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: As always, my articles are meant to facilitate your understanding. Readers are expected to form their own trading plan, do their own research and take responsibility for their own actions. Investing in common stock can result in partial or total loss of capital. Please implement due diligence and invest wisely.

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Galera Therapeutics And Amgen In Severe Oral Mucositis - Seeking Alpha

The Curious Case Of Enochian Biosciences: Value Out Of Thin Air – Price Target $1 – Seeking Alpha

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While everyone would love to have a cure for HIV, I have serious doubts that Enochian has much at all except a capital structure to greatly benefit it's board which owns about 65% of the company and can continue to grant options, stock and consulting agreements. Now miracles can happen, however we have not seen anything significant to date and currently the company is valued at $300m (fully-diluted) with less than $10m in cash. There are no scientific publications or data and the company is in pre-IND mouse model stage of development. I'll keep this brief. As with short thesis, I do not want to be accusatory or speculative. I believe the company should be worth about $50-100m or about $1-2 as are many companies at this stage with no tangible proof of concept and in need of cash. There are no legitimate healthcare specialized investors in the stock, only large asset managers with index funds. I believe the stock has bounced off of $3 to now $6 due to the relatively low float, the drastic increase in short-borrowing costs (4% to 35% and now 15% on some online brokers timed when commissions went away), and the lack of stock loan to short more shares perpetuating a short squeeze as short interest has gone from virtually zero in January to now about 800k as others in the market seem to have doubts.

Los Angeles based-Enochian (ENOB) was formed from a reverse stock merger in January 2018 with public company Dandrit which was a struggling Danish cancer immunotherapy company with a US exchange listing. The economics were 50/50 and with the Dutch company's shares tightly held and Enochian's predecessor private company (named Putnam Hills) only having a handful of large holders. The company now has a relatively low float of about 15m out of 46m shares and has flown under the radar. The legacy Dandrit shares are also closely held. There is no Wall Street coverage which is also curious for a company of its size. The lockup on the other half of about 65% of shares (18m) is February 2020. While the company includes cancer immunotherapy in its business description, it has moved quietly away from the legacy Dandrit science and focused more on HIV prevention and cures via gene therapy. Both gene therapy and cancer immunotherapy screen well as buzzwords but not all are worthy of premium valuations.

The main driver of value is a license from Weird Science LLC which is owned by company affiliates from the Enochian side. This license includes the use of combinatory gene therapy to promote genetic resistance and intracellular immunity HIV and for an in-vivo gene therapy to eliminate HIV infected T-Cells from the human body. The method Enochian is taking to cure HIV is similar to that taken by Sangamo, that is eradicating T cells with chemotherapy and transplanting CCR5 knockout stem cells so HIV can not enter T cells. Sangamo decided not to commit further internal resources to this because it could not consistently eradicate the virus and it was a cumbersome process which needed chemotherapy to work. Sangamo has since focused on rare diseases and is seeking an external partner for the HIV program. Enochian claims to get around (pg 12) Sangamo's pitfalls with more effective engraftment and gentler chemotherapy. However, we have yet to see anything that suggests this can work in a mouse let alone a human and it will take years and tens of millions of dollars to see if the virus in humans is fully eradicated and worth undergoing the treatment versus a virtually chronic disease treated daily with pills. There is a notable story of Timothy Brown (the "Berlin patient") who had leukemia, chemotherapy and CCR5 mutant stem cell transplant, but this result has yet to be replicated despite efforts like City of Hope and many, many others already in human trials-- highlighting the competition in the space. Should any of these 30+ efforts yield a cure in humans, it would seem that Enochian would face a greater challenge. I would also note that most of these are university programs or companies that are not worth close to $300m (ex-Gilead). Yet, the backbone Enochian intellectual property license sits on the balance sheet as an intangible at roughly $155m, creating inflated book value in my view due to the inflated amount paid for it, and the company is valued at $300m with only $10m in cash. This IP is solely from a patent (pg 14) owned by the Inventor (As the company calls him. I would like to avoid using names). I also have trouble finding a publication from the Inventor or Enochian on the use of autologous stem cells or anything biochemistry-related let alone any scientific data for their treatment from web searches, filings or their own web site. There just seems to be blind hope.

The company has managed to get by on cash from warrants (which are further dilutive with shares outstanding going from 36m to 46m from Sept 2018-June 2019) and an initial private round at the time of the merger of about $10m. It went from 3 to 8 employees this year--mostly entry level lab personnel and a new CFO who resides in Florida. Most of the SG&A (about $8m) is non-cash compensation $1.9m, salaries, public company expenses and leases. The management and board enjoy generous compensation and options agreements particularly for showing no results to date.

Source: Enochian 10-K

The R&D is curious as much of it (particularly in 2019) has been in the form of consulting agreements with entities controlled by Board members or with Board members themselves, some of whom are in labs in the same office building yet don't work for the company per se but hold large amounts of stock. For example, G-Tech Bio is an entity controlled by the affiliates of Weird Science LLC (curious why the consulting agreement was cancelled July 9, 2018 with Weird Science LLC and essentially transferred to this new G-Tech entity with a much greater fee). While consulting agreements were a condition to the merger and not abnormal, the amount of $1.5m relative to overall R&D of $2.4m is still eye opening.

Source: Enochian 8-K Exhibit

Interestingly, G-Tech Bio LLC has the same address as the Inventor's lab and physician practice, a non-profit. Now this could be completely sound as the Inventor along with Weird Science LLC are interested in the same research as Enochian but still makes me wonder what is being done at Enochian with less than $1m of R&D. This is how they can get by for 2 years on about $10m in cash and makes me wonder what they are doing with this $155m worth of intangible IP on the balance sheet, if it is indeed worth that much? And where are the results?

In the spirit of keeping this brief, I see this playing out in the following way. The company has pushed their pre-IND meeting with the FDA from Q3/Q4 2019 to now the "earlier part of 2020." The best they can press release is a mouse model that shows some freedom from HIV after using chemo and engraftment with a CCR5 knockout human stem cells but the duration will likely be unconvincing as we haven't heard anything and 2020 is a couple months away, in my view. The company attends Noble Healthcare conference in January but otherwise isn't very public outside an investor day in February 2019 where they did not have any scientific results. The lockup on the other half of the 36m shares lapses in February and there could be some selling pressure. Weird Science LLC basically got about $150m of value out of thin air assuming current prices for essentially getting a license which I believe is of questionable, unproven value. On top of this there needs to be a financing of some kind if they are to move forward in humans. I do not see the stock performing well absent the occasional short squeeze over the next 3 months and see the $300m or $6 a share dropping to $2-3 with a potential sell the news event if there is a press release on any kind. I do not see how this company is worth $6, and think it moves towards $1 if we see nothing by mid next year.'

Enochian proves me wrong by curing HIV in mice or non-human primates in a convincing way and does see the FDA for a pre-IND meeting in early 2020. They manage to do a financing for clinical trials at a price higher than $6 and generate enough excitement to maintain a higher valuation. Separately, from a trading perspective, there is a short squeeze as has happened in the past into company presentations, though I see these situations as temporary.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a short position in ENOB over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Update, November 4, 2019, 5:03 p.m.: This Disclosure has been updated from a previously incorrect version.

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The Curious Case Of Enochian Biosciences: Value Out Of Thin Air - Price Target $1 - Seeking Alpha