Har Grover, chairman and CEO

Closely-held Scientus Pharma hopes to go public in mid-year, possibly through a reverse takeover of a publicly traded shell company, following a successful $15.8-million private equity financing, which closed last week. 

"We hope to do a financing in the range of $40-million to $60-million, subject to favorable market conditions, concurrent with a potential reverse takeover," chairman and CEO, Har Grover, says in an interview with BioTuesdays.

Proceeds from the latest stock sale will be used to prepare for commercializing the company's line of pharmaceutical-grade cannabis products and for working capital.

"As a four-year-old private company, we have now raised $45-million and built a shareholder base of 17 institutions, which is pretty remarkable, and some 250 retail investors," he adds.

From a regulatory point of view, Health Canada currently permits the sale of cannabis oils and capsules, and Mr. Grover predicts Scientus can create value with its initial products in this sector.

He says Scientus has 12 products ready for launch over the next 18 months, of which three would be ready in the next six months.

The furthest along is the company's three soft gel caps for neuropathic pain, epilepsy and anti-seizures, and post-traumatic stress disorder (PTSD), which could be launched as early as April. "These currently fit within the product definition of what is approved under Health Canada's Access to Cannabis for Medical Purposes Regulations," he adds.

The company also is developing a delayed release gelcap, which Mr. Grover says is a minor amendment to regulations already in place and could be launched at the end of 2018, along with a transdermal patch; a sublingual capsule, which could be launched in 2019; a buccal spray, also with a 2019 launch target; and an extended release capsule.

Anticipated Timelines

"All of these products depend on Health Canada broadening its cannabis product definition," he adds.

Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the two most prominent cannabinoids found in cannabis. "THC is what gives you the high but when combined with CBD, the pycho-active component of cannabis is dampened," he points out.

In non-clinical terms, he says Scientus' pain formula is a balanced THC-to-CBD cannabinoid profile, epilepsy requires a higher CBD and lower THC cannabinoid profile, and PTSD requires a lower CBD and higher THC cannabinoid profile.

Mr. Grover explains that unlike traditional supercritical fluid extraction to treat cannabis with CO2, Scientus uses a continuous flow process with microwave energy to do its extraction in a single step. 

"Our continuous flow process results in an active pharmaceutical ingredient (API) that is 100% decarboxylated so that it is fully active and standardized," he contends. "That compares with supercritical fluid extraction, which results in a decarboxylated API of 60% to 95%."

Scientus' platform technology also can achieve 70% to 90% savings in energy costs and 40% savings in labor costs, compared with standard extraction methods. With its continuous flow process, he notes that the company can run up to six manufacturing cycles per day, compared with one-to-three for traditional extraction.

Proprietary Extraction Method

By the end of 2018, he is anticipating that the company will have leading metrics on extraction of cannabis.

Scientus has filed patent applications for methods of using microwaves to achieve 100% decarboxylation to create a standardized (API); apparatus design; and composition of matter.

The company expects to complete construction of its 45,000-square-foot pharma-grade plant by the end of March. Mr. Grover says the plant has a strategic advantage of housing both cultivation of cannabis and manufacturing of finished products, as well as lab space for R&D to ensure a long term and consistent supply of cannabis.

The plant also has a capacity to produce 200,000 gel capsules an hour, which Mr. Grover figures represents a potential daily revenue of $1-million based on an average retailing selling price of $1 per capsule.

"Ideally, our products are best suited for distribution by pharmacies and we are also pursuing branded opportunities with global pharma companies," Mr. Grover points out. Several national pharmacy chains in Canada are awaiting Health Canada approval to dispense medical marijuana. Ontario plans to distribute recreational marijuana through its beer and liquor retail outlets.

Target to Switch Sales from Existing Prescriptions

Pointing to new additions to its board, including Mike Cloutier, former CEO of AstraZeneca Canada; Greg Gubitz, a former SVP and general counsel of Biovail; Bruce Cousins, a former CFO of Arbutus Biopharma and Aspreva Pharmaceuticals; and Dr. Linda Maxwell, a prominent physician, entrepreneur and innovator, Mr. Grover says Scientus is building a "truly blue-chip corporate board."

This article does not constitute an offer to sell or the solicitation of an offer to buy any securities of HydRx Farms Ltd. (d/b/a Scientus Pharma Inc.) and shall not constitute an offer, solicitation or sale of any security in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Jason Flowerday, CEO

3D Signatures (OTCQB:TDSGF; TSXV:DXD; FSE:3D0) has reported positive results from a preliminary analysis of trial data for Telo-HL, its test for Hodgkin's lymphoma (HL) that is designed to personalize treatment for newly diagnosed patients.

"The results showed that the company's TeloView platform is able to distinguish, with a high degree of statistical significance, multiple differences between a patient group that responds to standard ABVD chemotherapy, and a group that relapses or is refractory to treatment within the first 12 months," CEO, Jason Flowerday, says in an interview with BioTuesdays.

ABVD is the standard-of-care, first-line chemotherapy regimen used in the treatment of HL that consists of doxorubicin, bleomycin, vinblastine and dacarbazine.

"We believe these results from the application of our TeloView platform to HL are so strongly positive, we can now even more confidently proceed with developing the final multivariate scoring model for the Telo-HL test to predict response at the individual patient level,” he contends.

The company remains on track to complete all phases of the test development and analytical validation by April 2018, he adds.

Mr. Flowerday says 3DS is considering making the test available broadly for research use and including it in HL clinical trials as part of a pharma services strategy that is in development.

"This milestone serves as an important proof of principle that our proprietary TeloView platform is highly robust and applicable to some tough cancers without effective biomarkers, and others which affect much larger patient populations," he adds.

3DS focused on HL because the treatment plan for this form of cancer is currently based on a trial and error system of testing different therapies to explore which, if any, a patient responds to.

Mr. Flowerday also says the HL test is the basis for accelerating development of other tests with major collaborators interested in TeloView's potential to personalize treatment for prostate cancer, which is the furthest along, for lung cancer, and for multiple myeloma.

"We have ongoing as well as newly planned pilot studies and collaborations with world oncology leaders that we expect to kick off later this year to build on the HL work and accelerate our other tests in development," he adds. "The ability to determine, via a blood test, which cancer patients should be prioritized for treatment would be a true game changer."

The TeloView platform builds on the foundational work done in Dr. Sabine Mai's Winnipeg laboratory to establish 3D telomere profiling as a novel biomarker platform. Dr. Mai is a director of 3DS and chair of its clinical and scientific advisory board. TeloView is supported by 25 clinical studies involving more than 3,000 patients and 20 different cancers, plus Alzheimer's disease.

Mr. Flowerday explains that 3DS' technology is based on the three-dimensional analysis of telomeres, the protective caps at the ends of chromosomes. The software platform measures genomic instability based on a 3D analysis of telomeres. Unlike many other technologies, TeloView is not dependent on sequencing mutations in the DNA to measure the stability of the entire genome.

3D Telomere Analysis

As a result, the TeloView software platform measures the content and configuration of the genome in the cell nucleus to determine its stability, and its correspondence to either the stage of a given disease, the rate of progression of the disease, how different diseases will respond to various therapies, and a drug's efficacy and toxicity.

"Our proprietary imaging and analysis software is designed to go beyond identifying whether a patient suffers from a specific disease or condition," he contends. "Instead, the TeloView platform is designed to inform clinicians and patients how to personalize treatment and best manage an individual's disease based on their unique TeloView Score."

Proprietary Software Algorithm

Currently, there is no biomarker that can predict the 15% to 20% of patients that will fail standard ABVD chemotherapy when first diagnosed with Hodgkin's lymphoma, he adds.

For the past year, 3DS has analyzed tissue samples from some 400 HL patients, who were subsequently treated with ABVD chemotherapy, contributed from hospitals in Canada and Europe. During the study, Mr. Flowerday says the company perfected its chemical assay, microscopy and processed all cell types through its TeloView algorithm.

Blinded data from the study were shared with 3DS' statistical partner, BioStat Solutions, who was unblinded and compared the TeloView data with the corresponding clinical outcomes for patients, and identified highly significant group differences across multiple TeloView parameters, Mr. Flowerday says. "BSSI confirmed our analysis as being extremely accurate."

Ronald Bromley, CEO of BioStat Solutions, says his company is excited to be collaborating with 3DS, "helping them ensure the quality of the data being used is to the highest standards, and that they are poised to deliver the best possible analysis of this predictive technology for HL treatment."

BioStat Solutions is now building a final predictive scoring model to test and determine the sensitivity and specificity of Telo-HL's performance in predicting ABVD response on further of HL patient samples based on their telomere profile.

"We have now reached a point where the data coming out of our TeloView platform is significant in telling us which patients are responders to ABVD chemotherapy and which patients will relapse to therapy," he adds.

In addition, 3DS intends to submit the completed test development and validation work for peer-review and publication in a top-tier medical journal in the latter half of 2018.

"We expect Telo-HL to benefit patients seeking personalized treatment and to provide significant cost savings to payers and insurers that are currently burdened with expensive treatments and procedures that may not be necessary if patients could be considered for more targeted and effective therapies at the outset of treatment," he adds.

Pipeline

Horst Zerbe, president and CEO

IntelGenx (OTCQX:IGXT; TSXV:IGX), which has initiated a proof-of-concept study with its Montelukast VersaFilm in patients with Alzheimer's disease, using a drug originally approved in 1997 for the treatment of asthma, is riding strong scientific rationale behind the repurposing program.

There are limited treatments available for Alzheimer's and, of those that are approved, none are disease modifying. 

"A recent paper published in the journal, Immunity & Aging, noted that montelukast has been shown to rejuvenate aged brains in an animal model and suggested that this leukotriene receptor antagonist may have a similar effect in humans," according to Horst Zerbe, president and CEO of IntelGenx. 

Leukotrienes are inflammatory molecules that white blood cells release during an asthma attack and montelukast has been shown to block leukotriene receptors that cause bronchial tubes to constrict. 

Evidence from Epidemiology / Comparative Effectiveness in Humans 

Because neurons and microglia, which act as the main form of active immune defence in the central nervous system, also express leukotriene receptors, IntelGenx is hoping to check if this type of signaling plays a role in brain inflammation.

The Phase 2a Montelukast VersaFilm trial is a randomized, double-blind, placebo controlled study that will enroll approximately 70 subjects with mild-to-moderate Alzheimer's disease across eight Canadian research sites. The primary study objectives will be to evaluate the safety, feasibility, tolerability, and efficacy of montelukast buccal film following daily dosing for 26 weeks.

"We believe that montelukast has the potential to be a true game-changer and are very excited to commence this trial," Dr. Zerbe says. The company expects to report interim results this summer and full results in the second half of 2018. 

In an earlier Phase 1 study, IntelGenx demonstrated that its oral film formulation of montelukast is safe and tolerable in healthy subjects, reduces the first-pass-effect and has 52% higher bioavailability, compared with regular montelukast tablets, demonstrating a clear advantage of delivering montelukast via film into the bloodstream. 

Montelukast VersaFilm™

IntelGenx's oral film of montelukast also crossed the blood-brain barrier, an essential feature for treating degenerative brain diseases.

After years of Alzheimer's research into brain amyloid as a cause of Alzheimer's, genetic and animal evidence now is pointing to the immune system as a central influencer in both hastening and ameliorating Alzheimer's progression. Because of this, many research groups are looking at ways to tamp down harmful inflammatory signalling. 

Signs of age-related cognitive decline include a slowdown in the creation of new brain cells, or neurogenesis, and neuroinflammation caused by activation of the brain's immune cells, or microglia. 

Elevated leukotrienes levels, which act as inflammatory mediators, have previously been reported in acute and chronic brain lesions and also in older animal brains, where they may be involved in neuroinflammation by recruiting and activating microglia. 

Research published in the peer-reviewed journal, Nature Communications, in 2015 showed that montelukast reverts brain aging and loss of cognitive functions in older rodents that have received the drug for six weeks at dosages fully compatible with those currently used in patients. 

The study, coordinated by Professor Ludwig Aigner of the Molecular Regenerative Medicine at the Paracelsus Medical University of Salzburg, Austria, involved several scientists in Europe, including Professor Maria Abbracchio at the University of Milan, Italy, and opens the possibility for the treatment of aging-related neurodegenerative diseases characterized by loss of cognitive functions, memory impairment and dementia.

Professor Maria Abbracchi

In an interview, Prof. Abbracchio points out that the brain is not secluded from the rest of the body and that its function is profoundly influenced by the presence of inflammation in other organs, such as the lung and brain.
"Ten-to-15 years ago, we anticipated that systemic inflammation can accelerate brain aging and increase the incidence of neurodegenerative diseases like Alzheimer's and Parkinson's," she adds.

Her research identified a brain receptor in the brain, GPR17, which demonstrated an action similar to leukotriene receptors. "For this reason, we tested montelukast for its ability to interact with GPR17 and found that montelukast acted as a blocker of this new receptor in a manner similar to its blocking ability of leukotriene receptors."

Prof. Abbracchio also points out that new research shows that inflammation can influence metabolism of brain amyloid, a long-held target for developing therapies to reverse the effects of Alzheimer's.

Prof. Aigner and colleagues treated five-to-10 young rats and a similar number of older rats with montelukast for six weeks. Learning and memory were significantly improved in aged rats, but no effect is observed in young animals. The treatment also was shown to reduce neuroinflammation and increase both the creation and functional use of new brain cells.

In addition, by using mouse cells genetically modified to generate less GPR17, the research group provided evidence that montelukast's effects most likely occurred by blocking the GRP17 receptor and may be responsible for the rejuvenation of the aged brain using montelukast.

The idea of repurposing montelukast for Alzheimer's disease is buoyed by its excellent safety record. However, the tablet poorly enters the bloodstream, which IntelGenx hopes it can overcome with a thin oral film formulation.

Even though Prof. Abbracchio isn't involved with the IntelGenx program, she contends that there is a strong scientific rationale behind developing montelukast to treat neurodegenerative diseases. She and Prof. Aigner also are discussing further preclinical research with montelukast. 

Early Clinical Evidence

In a research report last month, Ben Haynor, an analyst with Aegis Capital, notes Alzheimer's is a growing problem as the population ages, yet many therapeutic approaches have failed over the past several decades.
 
Of the Alzheimer's drugs that are available, nearly all are generic, yet about $7-billion is spent annually on psychiatric drugs in the U.S. for Alzheimer's patients. Branded Alzheimer's drugs have historically priced at $5,000-to-$7,000 a year, and a successful new compound could potentially double the market size, even if only 20% of patients received the drug. 

While there are scores of Alzheimer's drugs in development by everyone from Big Pharma to small-cap biotech and the failure rate of central nervous system drug development is higher than any other therapeutic class historically, Mr. Haynor points out that "success in this area would be richly rewarded."

He initiated coverage of IntelGenx with a "buy" rating and price target of $3, calling Montelukast VersaFilm "an exciting asset…with blockbuster potential."

Robust Product Pipeline

David Cory, president and CEO

Despite a failed Phase 2 trial in pulmonary arterial hypertension (PAH), Eiger BioPharmaceuticals (NASDAQ:EIGR) still has multiple shots on goal with its targeted therapies for orphan diseases, including a number of key milestones in 2018.

"While we are disappointed in the LIBERTY study outcome, we have always recognized that PAH is a complex disease and that this was a translational program, moving from animal data into human testing in the clinic," president and CEO, David Cory, says in an interview with BioTuesdays.

"Our pipeline was built specifically for this purpose, to reduce risk against a single binary event in order to avoid a situation where if one program fails, we would not implode and close our doors," he adds. "We have multiple shots on goal." 

PIPELINE AND MILESTONES

Mr. Cory said Eiger has already generated Phase 2 clinical proof of concept data in its two lead programs in hepatitis delta virus (HDV) and post-bariatric hypoglycemia (PBH).

Among Eiger's milestones this year is an end-of-Phase 2 meeting in February with the FDA to discuss Phase 3 registration plans for its HDV program. In the third quarter, the company expects to announce additional Phase 2 data in PBH and Phase 2 data in lymphedema.

HDV is the most severe form of human viral hepatitis and is always associated with hepatitis B virus (HBV) infection. Hepatitis delta is more aggressive, leading to more severe liver disease than HBV alone and is associated with accelerated liver fibrosis, liver cancer, and liver failure. At diagnosis, 50% of HDV patients already have cirrhosis. 

There are an estimated 110,000 HDV patients in the U.S., nearly twice as many in Western Europe, and no approved therapy anywhere in the world. 

Eiger has two complementary assets for HDV: lonafarnib, an oral drug candidate, which has completed Phase 2 testing, and pegylated interferon lambda (Lambda), which will complete Phase 2 testing in HDV in August. 

Ingrid Choong, senior director of clinical affairs and corporate development

"With lonafarnib and Lambda, we have the potential for multiple treatment options for physicians and patients," says Ingrid Choong, senior director of clinical affairs and corporate development.

The company has dosed more than 120 HDV patients across five Phase 2 studies at multiple international sites with lonafarnib, which has orphan drug designation in the U.S. and Europe. Recommended doses and regimens for registration have been identified. 

Specifically, all-oral lonafarnib in combination with ritonavir as well as a combination of lonafarnib, ritonavir and interferon demonstrated that more than 50% of patients achieved a greater or equal to 2-log decline or undetectable HDV RNA after 24 weeks of treatment. In addition, the majority of these patients had normalized alanine aminotransferase (ALT), a blood test that checks for liver damage. 

Eiger is also developing Lambda as a better-tolerated interferon for the treatment of HDV, alone and/or in combination with lonafarnib. Lambda was in-licensed from Bristol-Myers Squibb, where it was previously in development as a better-tolerated interferon for hepatitis C and B viruses, with more than 3,000 patients dosed in 17 clinical trials, producing a well-understood safety database. 

Dr. Choong explains that Lambda and interferon-alfa use the same signaling pathway and the same mechanism of action. However, Lambda is a Type III interferon, which binds to a unique Lambda receptor, compared with Type I alfa.

"Receptors for Lambda are much more focused in the liver, compared with interferon-alfa receptors, and, as a result, have the potential for fewer side effects." Those include less flu-like symptoms, psychiatric disorders and episodes of neutropenia, which reduces the body's ability to fight off bacterial infections.

Eiger has an on going Phase 2 LIMT study of Lambda monotherapy in HDV. Enrollment is complete with 33 HDV patients between sites in New Zealand, Pakistan and Israel. The company expects to complete the LIMT study in the third quarter of 2018.

Interim data from the LIMT HDV study was presented at the American Association for the Study of Liver Diseases in 2017 and demonstrated that of the 10-of-33 patients who had reached week 24 at the time of analysis, five patients were considered responders, achieving greater than a 2-log decline in HDV RNA, or undetectable HDV RNA, at week 24. 

Dr. Choong says the interim data suggests that Lambda is comparable to interferon-alfa in antiviral activity against HDV. In addition, investigators in the LIMT HDV study indicated that approximately 40% of their patients were previously treated with interferon-alfa, and they noted that Lambda was much better tolerated.  

"Observations of ALT flares is associated with HDV viral load declines [suggestive of] a vigorous immune response to therapy rather than hepatotoxicity or drug-induced liver damage," she adds. "We believe Lambda is a promising investigational agent, alone or in combination therapy for HDV."

At its end-of-Phase 2 meeting with the FDA in February, Eiger will propose a Phase 3 study with two treatment arms: an all-oral therapy of lonafarnib in combination with ritonavir as well as a combination arm of lonafarnib, ritonavir, and Lambda.

The proposed primary endpoint for registration in HDV will likely be similar to those used previously by regulatory agencies for approval of drugs currently marketed to treat HBV infection, including a reduction in viral load and normalization of liver enzymes. The secondary endpoint would be improvement in the histological activity as measured by liver biopsy.

Mr. Cory says the end-of-Phase 2 meeting with the FDA could be a transformative event, making Eiger a late-stage company, developing the first regimen for HDV.

In its post-bariatric hypoglycemia (PBH) program, Eiger has completed three clinical studies with exendin 9-39, dosing 36 patients, with statistically significant proof-of-concept data presented at medical conferences and published in peer-reviewed journals. 

PBH is a serious complication after bariatric surgery, which can achieve dramatic weight loss and resolution of Type 2 diabetes. However, certain hormones that regulate glucose metabolism often do not rebound after surgery. After every meal, these patients have a spike in insulin production and very quickly have their glucose degrade, become hypoglycemic and often fall into a coma and require immediate treatment in hospital emergency rooms.

"PBH patients often cannot work, cannot drive, cannot be alone, and need a caregiver," Mr. Cory says. "This is a dismal result to what should be a very positive surgical procedure."

In 2015, there were some 300,000 bariatric surgeries performed in the U.S. and Europe. The estimated prevalence of PBH is 70,000 in the U.S. and Europe and growing because of the popularity of bariatric surgery. There is no approved therapy for PBH.

Eiger is developing exendin 9-39, a GLP-1 antagonist, for PBH. GLP-1 is a hormone that is secreted by the lower small intestine that stimulates insulin secretion. PBH patients produce excessive levels of GLP-1, which causes a spike in insulin production, followed by hypoglycemia, after every meal.

"We know that physically blocking the GLP-1 receptor blunts this problem, attacking the root of PBH," Mr. Cory contends, adding that exendin 9-39 is designed to normalize insulin secretion and decrease symptoms of PBH, and "our Phase 2 program supports this hypothesis."

In the fourth quarter of 2017, Eiger initiated a 28-day Phase 2 study, known as PREVENT, with the objective of demonstrating durability of effect of exendin 9-39. Data from the study are expected in the third quarter of 2018, setting the stage for another possible end-of-Phase 2 meeting with the FDA.

"This is another transformative program that could take us from Phase 2 into Phase 3 within the next 12 months," Mr. Cory suggests.

In addition to HDV and PBH, Eiger is developing ubenimex for lymphedema, a state of vascular insufficiency, where the lymphatic system is blocked and proteinaceous fluid accumulates in the arm or leg, causing tissue remodeling. The disorder most often results after surgery or radiation, where lymph nodes are damaged or removed.

Last year, the peer-reviewed journal, Science Translational Medicine, published Eiger's extensive preclinical studies of ubenimex, demonstrating that modulation of the inflammatory mediator, leukotriene B4 (LTB4), improved experimental lymphedema. In addition, targeted reduction of LTB4 with ubenimex reversed edema, improved lymphatic function and restored lymphatic architecture in experimental models of lymphedema.  

Ubenimex has been marketed in Japan for over 30 years as an adjuvant to chemotherapy for a certain forms of leukemia, but has never been introduced in the U.S. or Europe. "This is a well-characterized and well-tolerated drug in its approved indication, with an established safety profile," Mr. Cory points out.

UBENIMEX FOR LYMPHEDEMA: PHASE 2 STUDY

Eiger has completed enrollment for the Phase 2 ULTRA trial of 54 patients with primary and secondary lymphedema in the lower limbs. Mr. Cory says the study has multiple primary and secondary endpoints, with an objective to show proof of concept that the LTB4 pathway, when modulated, can improve clinical lymphedema. Data readout for ULTRA is scheduled for third quarter of 2018. 

"Our focus is developing well-characterized drugs acting on newly identified or novel, validated targets," Mr. Cory says. "By systematically reducing the time and cost of drug development, Eiger hopes to more rapidly deliver medicines to patients with orphan diseases."