Dr. Agron Lumiani, leading German radiologist

After nearly a decade of R&D, Profound Medical (OTCQX:PRFMF; TSXV:PRN) is now conducting a pilot launch of its TULSA-PRO medical device to ablate tissue in localized prostate cancer within key European and other CE Mark jurisdictions ahead of full commercialization.

The first focal therapy with TULSA-PRO was successfully conducted at the ALTA Klinik in Bielefeld, Germany last week under the supervision of Dr. Agron Lumiani, a leading German radiologist and an early adopter of the use of MRI for prostate diseases imaging and biopsy.

Arun Menawat, CEO of Profound Medical, describes the pilot program as a great step forward in the journey to commercialize the TULSA-PRO system within Europe, and in building awareness about the technology as an attractive clinical option for patients with localized prostate cancer.

“We also believe it will act as a strong catalyst for further adoption of the therapy as we continue our penetration into other European and international markets,” Dr. Menawat adds. “We look forward to continue working with Dr. Lumiani, to address the unmet needs of patients who suffer from this disease.”

The TULSA-PRO system is an innovative, minimally invasive way to ablate tissue in patients with localized prostate cancer.

Arun Menawat, profound medical's CEO

The system uses MRI to carefully map out the unique shape of a patient’s prostate and plan the treatment best suited for their needs. The TULSA-PRO procedure then uses MRI guided, robotically-driven, therapeutic ultrasound, with real-time thermal feedback to accurately and precisely ablate the prostate tissue, all while preserving surrounding healthy tissue.

The same-day TULSA procedure is precise, accurate and offers low rates of serious or long-term adverse effects.

Profound is also sponsoring a multicenter, prospective FDA-registered clinical trial, TACT, which is designed to further demonstrate the safety and effectiveness of its technology. If successful, TACT is expected to support Profound's application to the FDA for approval to market TULSA-PRO in the U.S.

To support the rollout, the company has established strategic partnership/collaborations with two global medical device developers - Royal Philips and Siemens Healthcare.

In addition to ensuring compatibility of TULSA-PRO with their MRI platforms, Philips and Siemens are collaborating on the capital unit placements as well as joint marketing activities. Profound has publicly announced the sale of four commercial units.

Dr. Lumiani has been working with MRI technology since 1984 and founded the ALTA Klinik 11 years ago to focus on MRI diagnostics for prostate diseases. Since then, his clinic has performed more than 6,000 MRI examinations of the prostate.

“Our patients come from all over Germany and neighboring countries,” Dr. Lumiani says in an interview with BioTuesdays. “MRI examination of the prostate has become increasingly important for urologists.

MRI diagnostics, as a primary diagnostics, form the basis for detecting prostate cancer, even at an early stage. “MRI-guided and targeted prostate biopsy enables superior diagnostic clarity for prostate cancer, as it can ensure that the biopsy material comes directly from the suspected lesions,” he points out.

The TULSA-PRO system is an innovative, minimally invasive way to ablate tissue in patients with localized prostate cancer

“Although our biopsy method is MRI-guided and targeted, we also take out systematic tissue samples to give the patient maximum certainty in the result,” he adds. “The result of the biopsy helps the urologist to define the individualized treatment for each patient.”

Dr. Lumiani recalls that in 2009, his clinic developed a MRI-guided, targeted transgluteal transforaminal prostate biopsy. “It was important for me to find a way to access the prostate that did not involve going through the rectum, since that route leads to intestinal bacteria reaching the prostate, which requires a patient to take prophylactic antibiotics.”

The transgluteal transforaminal path to the prostate is ideal because access is sterile and painless, and enables reaching all suspicious lesions in the prostate, he adds. Ultimately, the rectum is left untouched, and other organs are not injured as a result.

Dr. Lumiani also has had positive results with transrectal HIFU (high-intensity focused ultrasound) as a focal treatment for the prostate.

But he contends that the advantages of the TULSA-PRO procedure are that it is done transurethrally, and that each localized tumor can be treated. The procedure is performed under constant real-time MR imaging, so that heat generation is accurately monitored throughout the entire treatment.

“With the TULSA-PRO, we preserve the rectal wall and the neurovascular bundle, and provide intra-urethral cooling which ensures the preservation of the urethral wall,” Dr. Lumiani explains. As a result, a patient’s anatomical structures and their functions, which run through the prostate, can be preserved.

Dr. Lumiani uses TUSLA-PRO for focal therapy of localized prostate cancer and for other diseases of the prostate.

“As a radiologist who has seen the advantages of MRI diagnostics for over 30 years, it is a great medical advancement to be able to offer our patients an MRI-guided prostate treatment,” he contends. “These prostate treatments are monitored by MRI the entire time. That means that the whole procedure, from the examination, to the biopsy, and straight to the treatment are MRI-guided in our clinic.”

In the future, Dr. Lumiani suggests that the radiologist and the urologist will work in closer collaboration. The radiologist provides the attending urologist with the diagnostic findings of the prostate, and the urologist then decides on how to proceed. Fusion biopsy, which is based on MRI diagnostics, will certainly be used more often in the future as well.

“Optimized MRI diagnostics, and the application of these methods, enables prostate tumors to be detected more often, and at the earlier stages than in the past,” he says.

“Overall, a greater number of patients receive maximum diagnostic certainty and their treatments can be customized precisely to their own needs, ensuring the best possible outcomes.” 

co-founder and CEO, enkateswarlu Nelabhotla (N. Venkat)

Closely-held Vyome Biosciences expects to enroll the final patient next month in a proof-of-concept clinical trial of its lead molecule for drug-resistant acne, VB 1953.

“Our product has the potential to be the first bactericidal antibiotic and anti-inflammatory topical gel for acne,” Venkateswarlu Nelabhotla (N. Venkat), co-founder and CEO, says in an interview with BioTuesdays. “We are the only company globally to address the issue of antibiotic resistance for skin pathogens.”

Vyome was established in 2011 to develop novel drugs for fungus infections in the scalp, but is now focused on developing molecules for drug-resistant skin infections.

In addition to acne, Mr. Venkat says Vyome has a deep pipeline of antibiotics, known as Dual Action Rational Therapeutics (DARTs) for multiple indications and a strong pipeline of clinically proven anti-fungal products based on Molecular Replacement Therapeutics (MRT). Nine patent groups, with some 300 patent applications filed globally, cover the company’s IP.

Only four antibiotics have been approved for the treatment of inflammatory acne in the U.S., of which clindamycin-based products are the most commonly used topically.

However, one-in-three people are resistant to clindamycin. “There has been very little innovation in this space for many years, making it a major unmet medical need, with a large and growing market,” he contends.

according to Mr. venkat, there is an unmet need and a growing market for antibiotic-resistant propionibacterium acne

Asked what differentiates VB 1953 from approved anti-acne medications, Mr. Venkat cites the anticipated patient response rates based on preclinical models; good anti-inflammatory properties; and “given the nature of the molecule and what we’ve seen in in vitro studies, we believe the probability of resistance developing in Propionibacterium acne is very, very low.”

Acne affects 240 million people globally. Some 100 million suffer from antibiotic-resistant acne, of which more than 10 million are in the U.S. alone.

“We are looking to address a potential $2-billion market for drug-resistant acne,” he points out. In addition, the same pipeline also addresses a $1.6-billion market of implant-related infections caused by Staphlococcus epidermidis, he adds.

In preclinical and in vitro studies, he says VB 1953 demonstrated excellent efficacy against antibiotic-resistant and-sensitive strains of Propionibacterium acne.

In January, Vyome released top-line results from a two-week Phase 1 study of VB 1953. The topical gel exhibited a promising dermal safety signal; was generally well tolerated, along with very low plasma concentrations; and displayed potential early signs of efficacy, with an early reduction in acne inflammatory lesions.

“These data are encouraging for patients with moderate-to-severe acne,” Mr. Venkat says.

Also in January, Vyome began enrolling up to 180 patients in a 12-week proof-of-concept clinical study of VB 1953 and expects to complete enrollment next month, with a data read out in August this year. The double-blind, randomized study will measure three efficacy endpoints: the number of patients with two points improvement in Investigator’s Global Assessment and a reduction in inflammatory and non-inflammatory acne lesion counts.

Vyome also plans to initiate a U.S. Phase 2b efficacy trial in the fourth quarter this year.

Beyond VB 1953, Vyome is developing a new generation of antibiotics, called DARTs, which have dual mechanisms of action against skin opportunist pathogens, making them candidates against the development of future resistance.

Last December, Vyome presented two posters at the Re-Entering Antibacterial Discovery and Development Summit in Boston. One detailed how its DARTs may have the potential to bypass and/or suppress antibiotic resistance for severe infections caused by orthopedic implants stemming from Staphylococcus epidermidis.

VB 1953 - PHASE 1 RESULTS SUMMARY

The second poster detailed the potential of Vyome’s library of novel antibiotics for skin opportunist pathogens and their low propensity to develop antibiotic resistance.

With its understanding of functional genomics, Vyome also has developed an advanced anti-fungal platform technology, known as Molecular Replacement Therapeutics (MRT), which not only impacts enhanced fungal killing ability to a known agent, but also allows for higher retention in deeper layers of the skin.

Mr. Venkat explains that MRT represents a novel way of changing the milieu of the fungi, which in turn disrupts the fungal membrane. “This technology can significantly enhance the efficacy of anti-fungal products,” he adds.

The company has commercialized two over-the-counter anti-dandruff products based on the MRT platform: a leave-on lotion and wash-off shampoo, and is in early development of a ketoconazole emulsion gel to treat skin Seborrheic dermatitis.

The program also includes several anti-fungal creams/lotions to treat recalcitrant Tinea infections, such as ringworm, athlete’s foot and jock itch.

Jon Lieber, cfo

Histogenics (NASDAQ:HSGX) expects to complete enrollment by the end of the second quarter this year in a Phase 3 clinical trial of its NeoCart biologic cell therapy and tissue engineering solution for knee cartilage regeneration.

“We believe that if we are successful in this Phase 3 trial, we have the potential to become the new standard-of-care in knee cartilage regeneration,” CFO, Jon Lieber, says in an interview with BioTuesdays.

“We believe that NeoCart is the only product on the market or in development that has a one-year primary endpoint for marketing approval, compared with other products, which based on available data, do not appear to show a difference to microfracture surgery, the standard of care, until well beyond one year,” he adds. “One-year superiority would represent a significant marketing advantage.”

In an earlier 30-patient Phase 2 study, NeoCart demonstrated a statistically significant response, compared with microfracture surgery, for relieving pain and improving joint function in patients with knee cartilage defects within one year of surgery, with 76% of NeoCart patients responding, compared with 22% for microfracture. Long-term follow up pointed to a positive trend persisting for at least five years following surgery.

according to lieber, Cartilage injury causes pain and loss of function, leading to lengthy unsatisfactory surgeries, or debilitating conditions later in age

Mr. Lieber explains that NeoCart is manufactured using the company’s proprietary tissue engineering platform that combines the patient’s own cells with the company’s scaffold, bioengineering and bioadhesives to create tissue ex vivo that is designed to mimic and integrate with the surrounding tissue after implantation into the knee.

In addition, he points out that NeoCart is a biologic, not a medical device, so the “regulatory pathway, clinical trial design and manufacturing process and know how represent significant barriers to potential competitors.”

Beyond knee cartilage injury, Histogenics believes that the NeoCart platform can be developed to treat defects at other joints, such as the ankle, shoulder, hip and toe, as well as other tissue types, such as ligaments and tendons.

Mr. Lieber suggests that existing surgical procedures and therapies require extensive recovery time, impede return to normal function and are often ineffective over the long term.

First line therapy for cartilage injury usually begins with orthoscopic debridement, which involves shaving the edges of bone and removal of loose cartilage. The procedure reduces pain but does not repair cartilage and often leads to a second procedure, microfracture surgery, which involves perforation of bone at the site of the lesion to stimulate cartilage regrowth. However, microfracture often results in lengthy rehab and variable outcomes. Some 30% of microfracture patients will require reoperation within two years.

“We have the potential to offer patients pain reduction and cartilage regeneration, with accelerated rehab and durable outcomes; physicians a fast and easy procedure, with favorable reimbursement and less time in the operating room; and payers a lower reoperation rate, with costs expected to be competitive with other autologous cell-based products on the market,” Mr. Lieber contends.

In addition, he says NeoCart has potential advantages, such as the one-year primary endpoint and focus on the smaller-lesion microfracture standard of care market over cell-based products now on the market, such as Vericel’s Carticel and MACI, a second-generation product, approved by the FDA last December.

Carticel is currently used as second-line rescue therapy following the failure of microfracture or other procedures. Unlike NeoCart, Carticel therapy injects a mixture of a patient’s chondrocytes into the site of injury and seals them using a covering, which can result in a more complicated surgery of one-to-three hours, compared with 30 minutes or less for NeoCart, as well as a longer recovery period and more varied results.

In addition, two common side effects of Carticel treatment are insufficient healing and bone overgrowth, which can lead to pain and joint stiffness. Mr. Lieber points out that no patient showed evidence of tissue overgrowth or knee stiffness in Histogenics’ previous Phase 1 and 2 studies.

neocart is designed to offer a complete solution for cartilage repair

In January, investigators published MRI and clinical outcomes data from NeoCart’s Phase 1 and 2 clinical trials in the American Journal of Sports Medicine. The data demonstrated significant improvement in cartilage quality over the first 24 months after treatment, with stabilization and maturation out to 60 months. In addition, improvements in cartilage quality were accompanied by consistent and statistically significant improvements in patient-reported clinical outcomes as early as three-to-six months after implantation, as compared to baseline.

According to Mr. Lieber, there is a strong correlation between untreated cartilage loss and osteoarthritis or total knee replacement. “We are targeting NeoCart to younger, healthy and active adults, with repetitive knee trauma and acute cartilage injury.”

Histogenics estimates that knee cartilage defects represent a significant market opportunity in the U.S., with an estimated 500,000 or more applicable corrective procedures each year. 

Mr. Lieber points out that the company’s Phase 2 study originally was designed to be an exploratory study, but the “strong data we obtained encouraged us to seek approval to move directly into a Phase 3 trial with a similar trial design.”

Like the Phase 2 study, Histogenics’ Phase 3 trial intends to evaluate whether NeoCart can outperform standard-of-care microfracture in improving patient pain and physical functions, as assessed by Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) score, at one year. Secondary endpoints include time to full weight bearing, reoperation rates and MRI analysis.

The Phase 3 trial, which is being conducted under a special protocol assessment from the FDA, will require an approximate 15-to-20-percentage point difference in responders between NeoCart and microfracture, he adds.

neocart phase 3 clinical trial

Histogenics is enrolling 245 patients in the Phase 3 trial, with 163 in the NeoCart treatment arm and 82 receiving microfracture. At the end of 2016, enrollment had reached 190-to-200 patients, with completion expected by the end of the second quarter.

“We believe this is the largest ever prospective trial of cartilage repair conducted in the U.S.,” Mr. Lieber contends, noting that so few products have been developed in the field because “historically, these trials have been difficult to enroll. The FDA wants to be sure that pain relief resulted from cartilage repair, not other corrective treatments.”

If the trial is successful, Histogenics hopes to file a Biologics License Application (BLA) in mid-2018, with possible marketing approval in the first half of 2019.

Mr. Lieber says Histogenics plans to build a scalable U.S. commercial infrastructure for NeoCart, with 40-plus sales reps, targeting high prescribing orthopedic surgeons. The company also will employ a small staff of medical liaison reps.  Due to the ease of the NeoCart procedure, the company can target large sports medicine surgeon markets with a small commercial infrastructure.

Outside the U.S., the company plans to partner the sales and marketing of NeoCart, initially in Japan. “We have been holding talks with the Pharmaceuticals and Medical Devices Agency in Japan and hope to share that feedback in the first half this year, which we expect will lead to discussions with potential partners,” he adds.

Mr. Lieber says that the company has a production-ready strategy and believes its fully integrated manufacturing facility in Massachusetts combined with the Phase 3 trial, which has the same design as the Phase 2 trial, have the potential to de-risk its BLA filing. The facility has state-of-the-art biologics, biomaterials and cell therapy capabilities.

“The expansion plan is also scalable so that for $10-million of capital, each additional manufacturing module has the potential to generate $75-million of revenue,” he adds. “Expansion will be based on demand but we have a modular strategy in place that matches up nicely with our regulatory strategy.”

Last year, Histogenics and Intrexon generated proof-of-concept data for next- generation, one-step allogeneic cartilage products to accelerate manufacturing and pipeline initiatives through a master cell line. “The data demonstrated our ability to make induced pluripotent stem cell-derived implants as measured by the same cartilage biomarkers as NeoCart,” Mr. Lieber says.  

The companies plan to meet with the FDA or other regulatory authorities this year to establish a development pathway.

In December, Swayampakula Ramakanth, an analyst with H.C. Wainwright, initiated coverage of Histogenics at “buy” with a price target of $3.50, saying that if the Phase 3 results hold up, NeoCart has the potential to become the best-in-class cartilage restoration treatment and replace microfracture as the first-line treatment of choice for knee cartilage injury. The stock closed at $1.84 on Friday.

“NeoCart may offer the potential for accelerated patient recovery, improved efficacy, a better safety profile, and can be used by more patients,” he added.

NEOCART PHASE 3 CLINICAL TRIAL BASED ON SUCCESSFUL PHASE 2 TRIAL

Dr. Terrence Norchi, president and CEO

Arch Therapeutics (OTCQB:ARTH) has multiple regulatory filings planned in the U.S. and Europe this year for its AC5 Topical Hemostatic Device as the biopharma company shifts to regulatory-stage footing ahead of commercialization.

“While we see a path to commercialization of AC5, we expect to remain a clinical-stage company as we develop subsequent products in our pipeline,” Dr. Terrence Norchi, president and CEO, says in an interview with BioTuesdays.

On the drawing board for 2017 is a filing for CE Mark approval in Europe, a 510(k) filing in mid-2017 for topical use in the U.S. and an investigational device exemption (IDE) filing in the U.S. to conduct a surgical trial for premarket approval (PMA) to use AC5 for internal use.

Dr. Norchi explains that AC5 is typically applied as a clear free flowing solution of self-assembling peptides that forms a scaffold or mesh gel of nanofibers within seconds of exposure to the ions naturally present in all bodily fluids, including blood, cerebrospinal fluid, and interstitial fluid.

Unlike many competitive products, he says AC5 conforms to irregular wound geometry, forming a barrier to achieve hemostasis, which then allows for normal healing while maintaining a clear field of vision directly into the wound area. Because it is not sticky or glue-like, it could be ideal for use in a range of open and closed procedures, he adds.

Arch’s preclinical pipeline includes several product applications with high medical need, including care of chronic cutaneous wounds and burns, prevention of surgical adhesions, sealing gastrointestinal anastomoses and ophthalmology. “We’ll advance the best product candidate where we see the most potential,” he suggests.

“Bleeding presents a significant clinical and economic burden. Any hole made in the body must be properly sealed and managed to allow for normal healing,” he adds.”

Bleeding also poses problems in surgical procedures and trauma, with loss of visual field and increased error risk, Dr. Norchi points out. Patients on anticoagulants and antiplatelet agents, also known as blood thinners, or those with co-morbidities, such as diabetes and renal disease, also are at increased bleeding risk.

“In our first clinical trial, AC5 has demonstrated it can establish a hemostatic barrier even in a patient taking blood thinners,” he contends.

dr. terrence norchi says,  AC5 conforms to irregular wound geometry, forming a barrier to achieve hemostasis, which then allows for normal healing while maintaining a clear field of vision directly into the wound area

Arch licensed the worldwide rights to the technology behind AC5 from MIT in Cambridge, MA. When adding patents covered by the license to its own patents and patent applications, Arch currently has more than 40 patients granted and pending to protect its intellectual property.

Dr. Norchi believes that existing products, such as gelatin, collagen, cellulose, polymers, thrombin and fibrin sealants, do not present ideal solutions to stop bleeding.

He says these products can be associated with a range of challenges, including unreliability, slow onset of action, handling restrictions, infections, negative inflammatory responses and healing problems. Some of the products can cost approximately $500 per application.

Many of the currently marketed products can take up to several minutes to stop bleeding, compared with often less than 30 seconds for AC5.

“What physicians want in a hemostatic barrier device is something that works quickly, easily, broadly and safely,” he points out, noting that this is the solution offered by AC5. “Data to date supports that our AC5 is biocompatible – or safe -  and the amino acids that it is made of are themselves made synthetically, rather than derived from humans or other animals.”

Last August, Arch reported results from its first clinical trial in humans, which met its primary and secondary endpoints. The study was conducted in Ireland with 46 patients, 10 of whom were on blood thinners. Each patient had two freshly excised, or bleeding, skin lesions: one treated with AC5 and one control lesion treated with saline.

Specifically, the median time to hemostasis of wounds in the AC5 treatment group, including those on blood thinners was less than 30 seconds, which was a statistically significant 41% faster than for those in the control group. Notably, the control lesions on patients taking blood thinners took more than three times longer to stop bleeding.

Dr. Norchi says the company is working on a next generation kit that would contain prefilled syringes, compared with the current AC5 powder that must be mixed.

Arch’s plan is to file for CE Mark approval as soon as possible this year. A 510(k) filing for topical use of AC5 in the U.S. has been advanced to mid-2017 from the earlier plan of late-2017.

The company also expects to file an investigational device exemption with the FDA this year for an AC5 surgical trial in order to obtain premarket approval (PMA) of the device for internal use.

"Our anticipated 510(k) filing focusing on external skin applications should present a nearer-term opportunity for AC5, compared with our previous plan of filing a PMA for all uses in the U.S.,” Dr. Norchi says.

“We anticipate that the potential benefit from an earlier 510(k) filing is significant in terms of business opportunity and technology validation,” he adds. “Our intent to file a PMA for internal use after completing the necessary human clinical work also remains intact."

Industry analysts suggest that the $3-billion global hemostat market, which is dominated by a relatively small number of global firms, will double over the next seven years.

“We believe those firms will be increasingly attracted to, if not threatened by, Arch’s AC5 hemostat as it continues to develop,” Roth Capital Partners analyst, Michael Higgins, wrote in an initiation report last month. He believes that AC5 has the potential to “revolutionize the hemostat market.”

Mr. Higgins rates Arch shares at “buy” with a 12-month price target of $3. The stock closed at $0.63 on Friday. 

pipeline potential: stasis and barrier applications - opportunities for arch and/or potential partners