On May 15, Rockwell Medical (Nasdaq: RMTI) announced the successful closing of a $35.0 million public offering of common stock. Along with the underwriter’s over-allotment option, net yield on the transaction was about $37.8 million. This financing removes a significant overhang from the stock and sets the stage for the release of Phase III CRUISE data in Q3 2013.

Financing Strengthens Rockwell’s Balance Sheet. On May 15^th, 2013, Rockwell Medical announced that it had set a price for a public sale of common stock. The Company issued 11,475,410 shares of stock at a price of $3.05/share to yield gross proceeds of $35.0 million. After expenses related to the transaction are deducted, Rockwell expects to receive $32.8 million.

On May 16^th, Rockwell announced that the underwriter of the sale exercised an over-allotment option to buy 1,721,311 shares of Rockwell common stock at a price of $3.05 to bring in an additional $5.25 million, of which the Company expects to receive about $5 million after deduction of the underwriter’s discounts.

We believe that the completion of this $37.8 million net transaction has removed the financing overhang from Rockwell Medical stock. In the months preceding the transaction, the stock had been under pressure from investors who were anticipating the need to raise capital. With the transaction in the books, the stock should show renewed strength in anticipation of Phase III data. We expect Rockwell will focus on expanding its current product line and, importantly, on completing their clinical studies and filing their New Drug Approval (NDA) for the approval of soluble ferric pyrophosphate (SFP).

SFP is Rockwell’s novel iron-delivery drug for the treatment of anemia in adult patients who are undergoing dialysis. The two pivotal Phase III clinical trials for SFP are nearing completion, with data expected from the first efficacy study in July. The money from this stock offering has put Rockwell on the path towards profitability.

CRUISE-1 and CRUISE-2 Pivotal Clinical Results Expected in Q3 and Q4. Rockwell Medical is currently conducting two Phase III efficacy trials for SFP. SFP is a unique iron compound that is delivered to the hemodialysis patient via dialysate, intended to replace the 5-7 mg of iron typically lost during a dialysis treatment. SFP is introduced into the sodium bicarbonate concentrate that subsequently is mixed into dialysate. Once in the dialysate, SFP crosses the dialyzer membrane and enters the bloodstream where it immediately binds to apo-transferrin and is taken to the bone marrow.  SFP mimics the way dietary iron is processed in the human body.  In completed clinical trials to date, SFP has demonstrated that it can safely deliver iron and maintain hemoglobin (Hgb) levels while decreasing ESA use, without any increase in iron stores.

The CRUISE studies are randomized, placebo-controlled, patient-blinded studies of SFP in patients with chronic kidney disease who are receiving dialysis. Each trial is intended to enroll up to 300 patients. The primary endpoint for each trial is mean change from baseline in Hgb, which is measured in two different ways. The first test is change in Hgb, measured weekly, over the course of up to 20 months. The second Hgb test is change from baseline during the last 8 weeks of the 12-month randomized treatment period. For patients who withdraw from the trial early, the measure will be change in Hgb during the last 1/6 of their treatment period. Secondary endpoints for the trials include various other measures of Hgb as well as transferring saturation (TSAT), ferritin, and the need for red blood cell or whole blood transfusions. CRUISE-1 was initiated in March 2011 and results are expected in July of this year, while CRUISE-2 was initiated in July 2011 and results are expected in October.

Strong PRIME Results Support Belief that Efficacy Will be Met in the CRUISE Trials. The CRUISE trials are based on the successful, well-executed Phase II program for SFP known as PRIME. That trial was placebo controlled, and the objective was for both groups to keep Hgb between 9.5 and 11.5 over 9-months.  All patients were eligible, under the same guidelines, to receive erythropoiesis-stimulating agents (ESA) and rescue iron in order to maintain Hgb in the target range. The protocol was executed perfectly and both groups completed the study with 10.5 Hgb. The placebo patients however, required a statistically significant 35% greater ESA dose during the study in order to keep their Hgb levels stable relative to SFP patients. These results are likely to translate into a statistically significant difference in hemoglobin levels between SFP treated patients and placebo patients in the Phase III CRUISE studies.

Upcoming Expected Milestones

• 2H13 – Commercial launch of Calcitrol expected.
• July 2013 – Top-line data from CRUISE-1 study.
• October 2013 – Top-line data from CRUISE-2 study.
• 4Q13 – File NDA for SFP iron delivery.
• 2013 – Reporting of complete data set from PRIME ESA-sparing study.
• 2013 – Possible license of SFP ex-US.
• 2H14 – Potential FDA approval and launch of SFP.

To read the full note, please click on the link below.

-ChondroCelect Sales Increased by 55%-

On May 14, 2013, TiGenix (TIG.BR) announced financial results for the first quarter of 2013 and provided a corporate update. The Company continues to see increasing revenue for ChondroCelect, and obtained reimbursement for the product in Spain. TiGenix ended the quarter with €6.8 million ($8.8 million) in cash on hand. In April it received the last tranche of €1 million of a soft loan to support the Phase III of lead product Cx601.

ChondroCelect Sales Continue to Grow, with a 55% Increase over the Prior Year’s Period. In Q1 2013,sales of the knee-cartilage regeneration product ChondroCelect increased to €1.04 million ($1.35 million), which represents a 55% increase over the first quarter of 2012. ChondroCelect revenue also increased 19% on a quarter-on-quarter basis, demonstrating that TiGenix continues to expand the market for the only approved cell therapy product that is approved in Europe. The sales are coming mostly from growth in Belgium and the Netherlands, where the product is reimbursed. TiGenix announced during the quarter that they had also obtained reimbursement in Spain, so sales should start to grow in that country. The Company is continuing negotiations to have the product reimbursed in France, Germany, and the UK.

TiGenix Reported Positive Data for Cx611 as a Treatment for RA. On April 22, 2013, TiGenix reported positive topline results from their Phase IIa study of Cx611, the Company’s stem cell therapy that was tested in patients with refractory rheumatoid arthritis (RA). The Company announced that Cx611 is safe and there was an initial indication of therapeutic efficacy. ACR20/50/70 scores, EULAR response, and DAS28 scores, commonly used in RA clinical trials, were used to monitor efficacy in patients. TiGenix reported that patients receiving Cx611 had higher ACR scores, better EULAR response, and higher DAS28 scores than patients receiving placebo.

Indication of Efficacy for Cx611 in Refractory RA. Cx611 is an allogeneic stem cell product that is derived from mesenchymal stem cells extracted from adipose tissue (eASCs). The Phase IIa trial was a single-blind, dose-escalation, placebo-controlled study where 46 patients were randomized to Cx611 plus disease-modifying antirheumatic drug (DMARD) and 7 were randomized to a placebo plus DMARD. Patients enrolled in the trial must have failed at least two biologic RA treatments, and have had RA for greater than 6 months.

Several metrics were used for monitoring efficacy in RA patients, including ACR scores, EULAR response, and DAS28 score. Patients in the Cx611 group had higher ACR scores, better EULAR response, and higher DAS28 scores those on placebo. The difference between the treatment and placebo arms was observed during the second and third monthly visits post-treatment, as well as the final visit. The number of patients with high scores and responses remained steady over the months following treatment, suggesting a long-lasting therapeutic effect. In contrast, patients receiving placebo showed an improvement in months one or two post-treatment, but regressed back to baseline by the third month, as one would expect in this very refractory population.

Overall, patients’ side effects were mild and transient, with only one serious adverse event reported out of 53 enrolled patients that led to discontinuation of treatment and there were no signs of hematological side effects or thrombosis. Safety results are consistent with safety data that the Company released as part of an interim analysis in December 2012. For a full accounting of the Phase IIa RA data, please visit www.lifesciadvisors.com/clients/tigenix.

Partnering Efforts Ongoing. TiGenix has announced an intention to find a commercial partner for Cx601, the Company’s developmental stem cell treatment for complex perianal fistulas. Patient enrollment for this Phase III program is continuing apace, and results are expected in mid-2014. With solid proof-of-concept data in hand, TiGenix is also in discussion with pharmaceutical partners who may be interested in licensing the rights to Cx611.

Financial Update. TiGenix reported that net cash used during the quarter was €1.4 million ($1.8 million), which was in line with expectations. The Company ended the first quarter of 2013 with €6.8 million ($8.8 million) in cash on hand. In April, the Company received the last tranche of €1 million of a soft loan to support the Phase III of lead product Cx601.

Upcoming Expected Milestones

• Ongoing – Partnering discussions for Cx611 and Cx601.
• 2H 2013 – Possible additional reimbursement decisions for ChondroCelect.
• 2H 2014 – Phase III results for Cx601 to treat complex perianal fistulas related to Crohn’s disease.
• 2014 – ChondroCelect is expected to become cash flow positive.

To read the full note, please click on the link below.

-Start of Pre-Clinical Work on Nanobody for Severe Allergic Asthma-

-Recent Financing puts Ablynx on Strong Financial Footing-

Report is Available for Download at: www.lifesciadvisors.com/clients/ablynx

On May 15, Ablynx (Euronext: ABLX.BR) announced financial results and a corporate update for the first quarter of 2013. The Company ended the quarter with €82.2 million in cash and equivalents, putting them in a strong position to execute on their development strategy for leading Nanobody therapeutics, which currently includes five clinical programs across multiple indications. Ablynx also recently announced the start of pre-clinical development with its anti-IgE Nanobody ALX-0962 for the treatment for severe allergic asthma.

Ablynx Starts Pre-clinical development of ALX-0962 to Treat Severe Allergic Asthma. On May 7, Ablynx announced the commencement of pre-clinical development for the anti-immunoglobulin E (IgE) Nanobody ALX-0962. The Nanobody is being developed for the treatment of severe allergic asthma, and the Company expects to start a Phase I study in the second half of 2014. ALX-0962 is a bivalent Nanobody with extended plasma half-life through the use of a Nanobody that binds to serum albumin. The Nanobody binds with high affinity to IgE, resulting in a very potent inhibition of IgE mediated allergic reaction upon allergen exposure. While this candidate is still in the early stages of development, it is further evidence of the broad applicability of the Nanobody technology.

Due to its dual mode of action, ALX-0962 has the potential to be the best-in-class, differentiated therapeutic to treat severe allergic asthma. The Nanobody is able to both bind strongly to IgE and also to displace receptor-bound IgE. It has the potential to address a broader patient population in a more effective, safe, and convenient way compared to currently available drugs, and could offer a treatment option to patients not eligible to current therapies.

ALX-0962 has Potential Advantages over Existing Drugs. Inhaled corticosteroids have long been the first line of treatment for severe allergic asthma. Unfortunately, steroids are not effective or not well tolerated for all patients, so better alternatives are always needed. ALX-0962 has a similar mechanism of action to Novartis and Roche’s approved treatment for severe allergic asthma, Xolair. Like Xolair, ALX-0962 targets immunoglobulin E (IgE),[1] however the Nanobody has numerous potential advantages. These include:

• Self-administration: Xolair is administered every 2-4 weeks and must be given at a doctor’s office, but ALX-0962 can be self-administered, saving time and money and making the treatment much more convenient for patients.
• Dual mode of action: While both Xolair and ALX-0962 target IgE, the Nanobody has a dual mode of action, able to both bind and displace bound IgE. This means that ALX-0962 has the potential to be a more potent and efficacious treatment option.
• Larger patient population: One of the drawbacks of Xolair use is that the dose must be specifically chosen based on serum IgE testing and body weight. Patients with high levels of IgE, high body weight, or certain combinations of the two are not eligible for treatment with Xolair.

Severe Allergic Asthma Market is Robust. Despite the fact that not all patients are eligible for treatment with Xolair, the treatment has strong sales and continues to experience robust growth. Marketing partners Novartis and Roche reported 2012 sales in excess of $1.2 billion, with 12% year-over-year growth. If Ablynx’ anti-IgE Nanobody ALX-0962 is shown to be a safe and effective alternative to Xolair and gains regulatory approval, it has the potential to capture a large portion of this market, including those who failed prior treatments, and also to expand the market to individuals not currently eligible for treatment.

Excellent ALX-0061 Data Suggests an Effective and Potentially Differentiated RA Drug. In February, Ablynx reported final, excellent 24 week safety and efficacy results from the Phase IIa study for ALX-0061 in patients with RA, which indicate that the anti-IL-6R Nanobody could potentially have a differentiating profile compared with the existing commercially available benchmark. Following the publication of these results, Ablynx started discussions with licensing partners to take the ALX-0061 program further in development and, in parallel, the Company is evaluating scenarios for carrying out the next phase of clinical development internally as an alternative strategy for creating value.

Clinical Progress for TTP and RSV Nanobody Candidates. Ablynx’ ALX-0081/ALX-0681 anti-von Willebrand Factor (vWF) Nanobody, caplacizumab, is currently in Phase II testing for the treatment of thrombotic thrombocytopenic purpura (TTP). Recruitment for the on-going worldwide, active at 55 clinical sites, trial is expected to complete recruitment of all 110 patients by the end of 2013. The Company did note that due to the rarity of TTP recruitment for this trial has been difficult.

The current goal for the anti-RSV Nanobody is to commence with a Phase II trial in infants in 2014. In order to meet regulatory safety requirements to start the study with ALX-0171, additional Phase I studies will be initiated during the course of 2013 in healthy volunteers. The Company has also initiated a pre-clinical study in juvenile animals, with the first results expected by the end of 2013.

Financial Results. Ablynx recorded revenue of €5.2MM, including contract income from on-going collaborations in the first quarter of 2013. Operating expenses decreased 28% to €12.1 million due to lower external R&D costs. The resulting net loss for the first quarter was €6.7MM compared to €6.2MM for the previous-year period.

Cash Position. Thanks to the successful financing activity completed in the first quarter, the Company had a positive net cash inflow of $25.2 million (€19.4 million), and ended the first quarter of 2013 in a strong financial position of $106.9 million (€82.2 million) in cash and equivalents. Ablynx raised $41 million (€31.5 million) through a private placement, allowing the Company to expand and diversify its shareholder base. For 2013, Ablynx maintained its net cash burn guidance of €20-25MM.

Expected Upcoming Milestones

• Complete recruitment of Phase II study for caplacizumab (anti-vWF) trial.
• Further development of anti-RSV (ALX-0171) – additional results by end of 2013.
• Start of Phase I clinical development for a number of partnered programmes.
• Announcement of next steps for ALX-0061 in RA including potential partner agreement.
• Licensing of clinical assets.
• New collaborations or expansion of existing relationships.
• Additional milestones from existing collaborations.
• Data from key feasibility studies.

Recent Elan Spin-Out is Well Capitalized with $120 Million in Cash

Lead Development Program, NEOD001 for Amyloidosis, is in Phase I Testing

www.lifesciadvisors.com/clients/prothena/

 LifeSci Investment Abstract

Prothena (NASDAQ: PRTA) is a biotechnology company developing a new class of antibodies that target misfolded, disease-causing proteins. Their lead drug NEOD001, which entered into a Phase I trial in April 2013, attacks proteins implicated in AL and AA amyloidosis. The second product, with Phase I trials planned for 2014, targets a key protein implicated in Parkinson’s disease. Prothena was spun off from Elan Pharmaceuticals at the end of 2012.

Key Points of Discussion

Prothena is a Well-Capitalized Biotechnology Company Developing Potentially Disease-Modifying Therapies for Amyloidosis, Parkinson’s disease, and Inflammatory Diseases. In August 2012, Elan announced plans to create a new spin-out entity to develop a number of promising candidates from the company’s drug discovery portfolio. The result of that spin-out was the formation of Prothena, which is listed on the Nasdaq exchange (PRTA) and is well capitalized with $120 million in cash (as of March 31, 2013). The Company has appointed a strong Board of Directors filled with successful biotech industry veterans and is now focused on the development of therapeutic antibodies to treat AL and AA amyloidosis (NEOD001), Parkinson’s disease (PRX002), and targeting melanoma cell adhesion molecule (MCAM) for the treatment of inflammatory diseases and cancer (PRX003).

NEOD001 is Highly Effective in Treating Amyloidosis in Mouse Models. In 2012, the NEOD001 antibody development program was granted Orphan designation by the FDA. Prothena’s IND application for NEOD001 has been accepted by the FDA for systemic amyloidosis, of which AL and AA are forms, and a Phase I clinical trial for NEOD001 in AL amyloidosis was initiated in April 2013. Administering the murine version of the NEOD001 antibody prolongs the life span of mice with clinical features of AA amyloidosis and shrinks the size of AL amyloidomas in mice relative to mice receiving injections of control antibodies. The multi-center Phase I clinical trial is designed to evaluate the safety and tolerability of NEOD001 in patients with AL amyloidosis and to determine a recommended dose for testing in Phase II trials.

New, Effective Treatments Would Greatly Expand the Amyloidosis Market. Current therapeutic options for amyloidosis are limited. There are no approved treatments for AL and AA amyloidosis that directly target potentially toxic forms of the AL and AA protein (amyloid). Current first-line therapies for AL amyloidosis are typically based on chemotherapeutic and anti-inflammatory agents and are administered for only short periods of time. Second line therapies for AL amyloidosis are not widely prescribed due to toxicity. Current treatments for AA amyloidosis include standard anti-inflammatories and drugs aimed at preventing failure of specific organs.

Existing treatments for both conditions reduce the source of the amyloid but have no direct effect on organ-deposited amyloids which often results in little or no organ improvement. Moreover, all existing treatments for both types of amyloidosis eventually lose their effectiveness, limiting market potential and making the diseases uniformly fatal. Although some chemotherapy treatments have shown effectiveness in eliciting a B cell response in amyloidosis patients, these drugs do not address the amyloid deposits. By contrast, NEOD001 targets the pathenogenic amyloid fibrils that, when not treated properly, accumulate in organs, leading to organ dysfunction and eventually kill patients. NEOD001 has the potential to expand the size of the market by altering the course of the disease, converting amyloidosis into a chronic but treatable condition.

PRX002 is Effective at Improving Motor Control and Cognitive Functioning in Mouse Models of Parkinson’s disease. Prothena’s second development program is for the antibody PRX002 as a treatment for Parkinson’s disease. PRX002 is currently being tested further in animal models. A Phase I clinical trial is expected to begin in 2014. Evidence suggests that symptoms of Parkinson’s disease result from cellular damage and death caused by a-synuclein (a-syn) deposits in the brain. Preclinical studies have shown that administering the murine version of PRX002 to mice genetically engineered to model the disease clears a-syn deposits from neurons, preserving neuronal functioning and cognitive performance. While these transgenic mice initially have impaired motor control and spatial memory, their performance on these measures improves following chronic administration of the drug.

New Disease-Modifying Therapies may Expand the Parkinson’s Disease Market that is Currently Expecting only Modest Growth. The market for Parkinson’s disease has been estimated to be worth between $1.7 to $2.2 billion in 2012 in the US and the largest countries in Europe. Current treatments target only the symptoms of the disease, leaving the underlying causes unaddressed. Loss of exclusivity on top-selling, symptom-targeting, products such as Orion/Novartis’ Stalevo and Teva/Lundbeck’s Azilect, along with the resulting generic encroachment, is likely to be the major driver of the market over the next decade. Expectations are for the market to stay flat, or shrink slightly, in the US, while growing modestly in Europe. Innovative products with disease-altering characteristics, including immunotherapies such as PRX002 are clustered at stage I and II in development. If they make it to market, these products could significantly alter the treatment landscape and lead to significant market expansion.

PRX003 is a Preclinical Candidate in Development for Inflammatory Conditions and Cancer. Melanoma cell adhesion molecule (MCAM) is a protein that allows certain cells travelling in the blood stream to leave the circulation and enter tissues. Its activity contributes to inflammatory diseases and metastatic cancers. PRX003 has been shown to be effective in reducing secondary relapses in a murine EAE model often used to assess potential MS therapies. Prothena has developed specific and novel antibodies that block MCAM-mediated cell trafficking and that are currently being tested in additional animal models of inflammatory conditions and cancer.

Financial Outlook

2012 Financials – Prior to Dec 31, 2012, the Prothena Business consisted of a substantial portion of Elan Corporation’s former drug discovery business platform, which historically operated as part of Elan and not as a separate stand-alone entity. The carve-out financial results for the period from January 1 to December 21, 2012 reported here have been prepared in accordance with U.S. GAAP, but do not necessarily represent the financial position or results of operations of Prothena had it been operated as a separate independent entity.

For Q4 of FY2012 Prothena reported a net loss of $12.2 million vs. $9.6 million for Q4 of 2011, and a net loss of $41.4 million for the full year of 2012 vs. $29.7 million for the full year of 2011. Net loss per share for Q4 and full year of 2012 was $0.82 per share and $2.84 per share, respectively, compared to a net loss of $0.66 per share and $2.05 per share for the respective prior periods.

Recent Financing Activity/Cash. Prothena was spun off from Elan on Dec 20, 2012 with initial capital of $125 million and no debt. The Company expects a cash burn of $34 to $40 million for 2013, ending the year with approximately $88 million. Thus, Prothena has a strong cash position with the ability to fund operations for more than 3 years, potentially into mid-2016. The 2013 cash burn is primarily driven by an estimated net loss of $36 to $42 million, which includes an estimated $2.5 million of depreciation and share-based compensation expense. The Company intends to use the anticipated 2013 spend to advance patient enrollment and dosing at multiple sites for its NEOD001 Phase I clinical trial, complete IND enabling toxicology studies for PRX002, select a first indication for PRX003, and further advance its discovery programs.

Expected Upcoming Milestones

NEOD001 Milestones:

• 2013: Continue to enroll patients at multiple sites
• 2014:  Initiate Phase II and announce topline Phase I trial results

 PRX002 Milestones:

• 2013: IND enabling studies and pre-clinical safety testing
• Q1 2014: IND filing expected
• 1H 2014: Initiate Phase I clinical program in Parkinson’s

 PRX003 Milestones:

• 2013: Manufacturing and select initial indication
• 2014 Pre-clinical safety testing
• 2015: IND filing expected
• 2015: Initiation of Phase I clinical trial expected

To download the full initiation report, please click the link below.

Report is Available for Download at: www.lifesciadvisors.com/clients/celsus/

On May 8, Celsus Therapeutics (OTCQB: MRRBY) announced interim results from the 2% dose cohort in their Phase II trial of MRX-6 to treat allergic contact dermatitis (ACD). Patients experienced a statistically significant 56% improvement in symptoms from baseline for their treated hand or forearm compared to a 24% improvement for the control hand or forearm (p<0.001). This improvement is comparable or better than that achieved in similar recent dermatitis trials.

MRX-6 Produced Significant Patient Benefit in Phase II Testing. MRX-6, the leading clinical candidate in Celsus’s development pipeline, is a member of proprietary compounds known as multi-functional anti-inflammatory drugs or MFAIDs. It acts via the inhibition of sPLA2 and by enriching cell surface glycosaminoglycans and is formulated as a topical cream. The results announced by Celsus indicate that MRX-6 is a promising non-steroidal alternative for patients with ACD. The data released on May 8 includes 30 patients assigned to treatment with the 2%dose of MRX-6 .The data released indicates a statistically significant improvement in the patients’ total Physician’s Visual Assessment (PVA) score, which takes into account common signs and symptoms including scaling, redness, pruritus (itching), fissures, and dryness. Patients experienced a 56% improvement in PVA score on their MRX-6  treated hand/forearm compared to 24% for the vehicle-treated, control hand/forearm (p<0.0001). 70% of patients experienced a clinically significant benefit on the treated hand/forearm, defined as a minimum 50% reduction in signs and symptoms from baseline. Notably, this clinical benefit was consistent across study sites, patient baseline PVA score, and symptom sub-groups. MRX-6 was found to be safe and well tolerated, with no adverse events reported in the trial.

Symptom-Level Efficacy Results. In addition to the topline results just discussed, Celsus released data specific to each of the five signs and symptoms that were measured in the trial, as well as data from the total PVA. These data are detailed in the table in Figure 1. The table unambiguously shows a greater improvement of symptoms in the MRX-6 treated hand/forearm than in the control hand/forearm. The difference was statistically significant for all symptoms.

Please Click the link below to read the full report.

-Potential Best-in-Class Oral Testosterone Replacement Therapy Poised for Phase III Trial-

-Pipeline Candidates include Once-Daily Oral TRT and Potential First Oral Drug for the Prevention of Preterm Birth-

Report is Available for Download at: lifesciadvisors.com/clients/lipocine

LifeSci Investment Abstract

Lipocine Incorporated is a biopharmaceutical company dedicated to becoming a leader in certain sectors of men’s and women’s health. The Company’s lead product candidate LPCN 1021 is an oral testosterone replacement therapy that has successfully completed a Phase II trial. In December 2012, Lipocine announced that the FDA has cleared LPCN 1021 to begin Phase III testing.

Key Points of Discussion

Overview of Lipocine’s Strategy. Lipocine is focused on becoming a leading men’s and women’s health company by leveraging its proprietary delivery technologies to develop oral prescription products and improve patient compliance. Lipocine is using its Lip’ral Promicellar Technology to enhance the absorption of poorly soluble drugs such as testosterone undecanoate. This technology can be used with hydrophobic drugs to create an optimal dispersed phase in the gastrointestinal (GI) tract, providing effective drug transport across the aqueous barrier layer in the GI tract and subsequent absorption into the bloodstream. The company’s lead drug candidate is LPCN 1021, an oral testosterone replacement therapy (TRT) for males with hypogonadism. This program is poised to enter Phase III testing under an FDA approved plan. Lipocine is also developing LPCN 1111, a once-daily TRT which has completed Phase I pharmacokinetic studies. LPCN 1107, an orally bioavailable version of hydroxyprogesterone caproate for the prevention of pre-term birth, has completed pre-clinical testing and is ready to enter a Phase I trial.

LPCN 1021 is a Potential Best-in-Class Oral TRT. LPCN 1021 has undergone seven clinical studies to date, testing the treatment in 158 hypogonadal men with no significant adverse events (AEs) reported to date. LPCN 1021 Phase II studies have convincingly demonstrated excellent pharmacokinetics as well as clinical efficacy. Four ascending doses were used and pharmacokinetic profiles were obtained pre- and post-therapy. Optimal testosterone undecanoate dose was found to be 225 mg twice daily (BID). In this dose cohort, LPCN 1021 exceeded FDA serum testosterone requirements, with 83% of patients achieving the pre-defined average concentration and 69% in the lower bound, 95% confidence interval. The FDA requires that at least 75% and 65% of patients achieve these endpoints, respectively. The 225 mg dose met all the secondary endpoints related to C_max excursions that the FDA requires for TRT products. Regarding safety, there were no major adverse clinical events or significant changes in liver enzymes or HDL/LDL, both of which have been associated with prior oral testosterone therapies.

Lipocine has received FDA clearance to begin a pivotal Phase III clinical trial of LPCN 1021, which would support marketing approval. The proposed Phase III clinical trial will enroll 300 patients randomized to treatment with LPCN 1021 or active control. Patients in the treatment group will receive 225 mg twice daily with full pharmacokinetic profiles obtained at 3 weeks. Therapy will then be titrated for those patients who fall outside pre-specified serum testosterone levels. Therapy administration will proceed for three more weeks followed by a second round of dose titration at week 7. The efficacy portion of the trial will last approximately 13 weeks with the primary endpoint of average serum testosterone levels.

The FDA requires that at least 75% of patients have an average serum concentration (C_ave) of 300-1140 ng/dL. Important secondary endpoints required for approval include maintenance of maximum serum testosterone concentration (C_max) below 1500 ng/dL in at least 85% of subjects, C_max between 1800-2500 ng/dL in fewer than 5% of patients, and no patients with C_max greater than 2500 ng/dL. Planning for the trial is currently under way and a lead CRO candidate has been identified. Enrollment is anticipated to commence in the third quarter of 2013 with completion of the trial and subsequent NDA filing expected in early 2015.        

LPCN 1111 is a Potential Once-Daily TRT. LPCN 1111 is a once-daily, novel prodrug of testosterone which uses the Lip’ral technology to enhance solubility and improve systemic absorption. In a single dose (95 mg of testosterone equivalent), randomized, open label, crossover study in 8 postmenopausal women, pharmacokinetic results suggested once-daily dose is feasible. The next steps in development for this program include a pre-IND meeting with FDA followed by a Phase II proof-of-concept study in hypogonadal men.

LPCN 1107 for the Prevention of Preterm Birth. LPCN 1107 has the potential to become the first orally bioavailable hydroxyprogesterone caproate indicated for the prevention of preterm birth. The product has completed a 28-day repeat dose toxicity study in dogs. A Pre-IND meeting has also been completed with the FDA, paving the way for an early-phase proof-of-concept study in pregnant women with a history of preterm birth.

Financial Discussion

Lipocine is a private company and is currently seeking a private placement of $30 million. Proceeds will be used to advance LPCN 1021 into a phase III clinical study and subsequent NDA filing (approximately $22 million), as well as to initiate proof-of-concept studies with LPCN 1111 and LPCN 1107 (approximately $3 million). The remaining proceeds will be used for general and administrative purposes.

Expected Upcoming Milestones

• Q3 2013 – Complete of manufacturing of clinical supplies for LPCN 1021 Phase III trial.
• Q3 2013 – Initiate Phase III clinical trial of LPCN 1021 in hypogonadal men.
• Q1 2014 – Complete enrollment in LPCN 1021 Phase III clinical trial.
• Q2 2014 – Efficacy analysis of LPCN 1021 Phase III clinical trial.
• Q1 2015 – Final results of LPCN 1021 Phase III clinical trial.
• Q1 2015 – Potential LPCN 1021 NDA filing with the FDA.

The full Initiation of Coverage Report can be downloaded below:

-Positive Phase I/II Results of   NurOwn^TM Cell Therapy for ALS Presented at AAN-

Report is Available for Download at: www.lifesciadvisors.com/clients/brainstorm/

LifeSci Investment Abstract

BrainStorm Cell Therapeutics (OTC QB: BCLI) is a biotechnology company with a unique approach to treating debilitating neurodegenerative diseases. Positive Phase I/II safety and efficacy results were announced in March 2013 for the Company’s stem cell technology as a treatment for amyotrophic lateral sclerosis (ALS). A new Phase IIa study was initiated in December 2012 and a second Phase II trial is slated to begin in late 2013.

Key Points of Discussion

Promising Phase I/II ALS Data Presented at AAN. BrainStorm announced results of their Phase I/II clinical trial of NurOwn^TMautologous stem cell therapy for amyotrophic lateral sclerosis (ALS) at the 2013 Annual Meeting of the American Academy of Neurology (AAN). BrainStorm’s presentation was specifically chosen for expedited release in the Emerging Science Session at the conference. The trial met the primary endpoints of safety and efficacy. No serious treatment related adverse events were reported from the 12 patients enrolled, and 50% of the patients reported no adverse events at all. The study was an interventional, non-randomized trial to monitor safety and tolerability of the NurOwn technology in patients with ALS. Efficacy was measured by changes in the rate of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) decline and rate of forced vital capacity (FVC) decline when comparing the 3 months pre-treatment with the 6 months post-treatment. Significant decreases were reported in the rate of ALSFRS-R decline (p=0.0013) and FVC decline (p<0.0001) in the intrathecal (IT) transplanted patients. These results indicate a trend toward possible stabilization of the disease. The results also support the Phase IIa trial in Israel that began in December 2012 and the planned Phase II trial in the US.

NurOwn is a Platform Stem Cell Technology with the Potential to Treat Neurodegenerative Diseases. NurOwn is a novel stem cell technology that BrainStorm has developed using adult mesenchymal stem cells (MSC) derived from the patient receiving the treatment. These autologous cells are differentiated into neuron-supportive cells that secrete neurotrophic factors (NTF) such as glial-derived neurotrophic factor and brain-derived neurotrophic factor, thus they are referred to as “MSC-NTF” cells, or NurOwn. Autologous adult stem cell therapy is free of the immune-related issues associated with allogeneic approaches that use cells from donors, as well as the ethical issues that are raised with the use of embryonic stem cells.

BrainStorm to Initiate A Phase II Trial with Partners Massachusetts General Hospital, UMass Medical Center, and the Mayo Clinic. BrainStorm is preparing its IND application to the FDA for approval to begin a Phase II trial in the US using NurOwn cell therapy to treat patients with ALS. Three prominent institutions, the Mayo Clinic, Massachusetts General Hospital, and UMass Medical Center, have agreed to conduct the trial once IND approval is granted. The collaboration with institutions of this caliber highlights the interest in the specific approach that BrainStorm is using to treat neurodegenerative diseases. The Company also recently announced that Dana-Farber Cancer Institute will provide cGMP cleanroom facilities for the production of the NurOwn cell therapy for the two Massachusetts-based centers.

Phase IIa Dose-Escalating Trial Initiated in December 2012. Following promising data from Phase I/II trials using NurOwn cells, BrainStorm is conducting a Phase IIa study at the Hadassah Medical Center in Israel to continue testing the effects of MSC-NTFs in ALS patients. The trial is a prospective, open label, dose-escalating study in patients experiencing early-stage ALS for no more than two years. The primary endpoint is safety and tolerability of a single injection of MSC-NTF cells at three different dosing levels. Secondary endpoints include changes in the rate of disease progression monitored by ALSFRS-R, changes in muscular strength, changes in bulk muscle, changes in upper and lower extremity circumference, and changes in electromyographic parameters. A total of 12 patients will receive single intramuscular (IM) and intrathecal (IT) injections of MSC-NTF cells. Patients will be observed on a monthly basis following treatment and monitored for safety and exploratory efficacy.

ALS Market Outlook. There are an estimated 30,000 people living with ALS in the United States,^, with an estimated 5,600 Americans being diagnosed each year. In advanced cases, treatment costs can be as high as $200,000 a year, representing an aggregate direct cost to the health care system of more than $6 billion per year. Patients with ALS have an urgent need for effective treatment options, as there is only a single FDA-approved drug to slow disease progression, and its efficacy lasts 2-3 months.

BrainStorm Targets Debilitating Neurodegenerative Diseases. While BrainStorm is positioned to be a strong competitor in the ALS treatment market, the company plans to expand its cell therapy pipeline to target other neurodegenerative disease indications in which patients also have a loss in neuronal cell health and function.

Financial Discussion

2012 Annual Results. BrainStorm has received $533,000 in 2012 and an additional $393,000 in 2013 to date as part of a grant from Israel’s Office of the Chief Scientist (OCS) to develop NurOwn, and will receive an additional $1,050,000 in the future. The Company had total operating costs and expenses of $3.5 million in 2012 compared to $3.9 million in 2011. The decrease is attributable to lower general and administrative costs. A loss of $0.02 per share was reported for the fiscal year 2012.

Cash Position and Financial Outlook. BrainStorm had $4.1 million at the end of 2012, out of which $1.3 million was in cash and cash equivalents, and $2.8 million was in short-term deposits, as compared to $1.9 million at the end of 2011, which was comprised of cash and cash equivalents only.

Expected Upcoming Milestones

• Q3 2013 – Complete treatment of Phase IIa ALS trial patients in Israel
• Q4 2013 – Launch Phase II trial in the United States using NurOwn to treat ALS

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-Cx611 is Save and Appears to be Effective based on ACR, EULAR, and DAS28 Responses-
-Promising Data Collected in Refractory Patient Population-

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On April 22, 2013 TiGenix NV (NYSE Euronext: TIG.BR) reported positive results from a Phase IIa study in patients with refractory rheumatoid arthritis using Cx611, which employs allogeneic adipose-derived stem cells. The data demonstrates that Cx611 is safe, and an initial indication of therapeutic efficacy was also reported.

TiGenix Reports Successful Phase IIa Trial of Cx611 in Patients with Refractory Rheumatoid Arthritis. TiGenix has completed a Phase IIa clinical trial with Cx611 to monitor safety and preliminary efficacy in patients who have failed prior treatments for rheumatoid arthritis (RA), including treatment with biologics. The company announced that Cx611 is safe and there was an initial indication of therapeutic efficacy. ACR20/50/70 scores, EULAR response, and DAS28 scores were used to monitor efficacy in patients. These metrics are commonly used to establish a clinical benefit in patients with RA. TiGenix reported that patients receiving Cx611 had higher ACR scores, better EULAR response, and higher DAS28 scores than patients receiving placebo. The difference between the treatment and placebo arms was observed during the second and third monthly visits post-treatment, as well as the final visit. The number of patients with high scores and responses remained steady over the months following treatment, suggesting a long-lasting therapeutic effect. In contrast, patients receiving placebo showed an improvement in months one or two post-treatment, but regressed back to baseline by the third month, as one would expect in this very refractory population. These results are exciting considering that the enrolled patients are especially difficult to treat, with a mean time since diagnosis of 15 years, and patients having taken a mean of three previous non-biologic DMARDs and three biologics.

Cx611 Trial Design. Cx611 is an allogeneic stem cell product that is derived from mesenchymal stem cells extracted from adipose tissue (eASCs). TiGenix has developed methods for generating these cells in high numbers from donated cells. The trial was a single-blind, dose-escalation, placebo-controlled study where 46 patients were randomized to Cx611 plus disease-modifying antirheumatic drug (DMARD) and 7 were randomized to a placebo plus DMARD. Patients enrolled in the trial must have failed at least two biologic RA treatments, and have had RA for greater than 6 months. Patients were assigned to one of three cohorts, which were designed as shown in Figure 1. The cell therapy or placebo was administered intravenously on day 1, 8, and 15. Lactated Ringer’s solution was used as the placebo.

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On April 10, 2013 Innate Pharma (Euronext: IPH.PA) announced new pre-clinical data at the 2013 American Association for Cancer Research (AACR) Annual Meeting for the IPH41 antibody targeting killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2), which is overexpressed in T lymphoma/leukemia subtypes. The company also presented pre-clinical data on April 12, 2013 at the Molecular Pattern Recognition Receptors Meeting for IPH33, targeting inflammation via the Toll-like receptor 3 (TLR3).

Targeting KIR3DL2 Induces Tumor Cell Death In Mice Xenografts and Ex Vivo Patient Samples. Innate presented data for the IPH41 program at the 2013 AACR with two candidate monoclonal antibodies (mAbs) that target KIR3DL2. Using three different models to assess the cytotoxic effects of the mAbs, the company reported a strong ability of the mAbs to directly target KIR3DL2-expressing tumor cells and cause cellular death. One experiment monitored NK cell-mediated death in cancer cells harvested from 2 patients with Sézary syndrome. Adding a KIR3DL2 mAb induced cell death in both patient samples. Similar antibodies are also being developed for diagnostic purposes and as biomarkers to more effectively identify patients with cancers that are characterized by KIR3DL2 overexpression.

Antibody Targeting Toll-like Receptor 3 Efficiently Blocks Signaling. At the 2013 Molecular Pattern Recognition Receptors Meeting, Innate presented the IPH33 program to develop antibodies targeting the receptor TLR3. A humanized antibody has been generated and was shown to efficiently target TLR3. The candidate antibody is currently being validated and the company intends to seek a partner for further development of the program.

Treating Inflammation by Inhibition of the Toll-Like Receptor 3. Innate has a proprietary program to develop an inhibitory antibody targeting TLR3, a receptor for double-stranded RNA. The receptor is most abundantly expressed in a subset of dendritic cells. Expression is also observed in epithelial cells from several tissues that are potentially exposed to pathogens, such as lung and colon. Activation of the receptor leads to a release of pro-inflammatory cytokines and chemokines. Activation is known to occur due to viral infection of a cell, but also due to the release of RNA from necrotic cells. The aberrant expression of the receptor, suggesting a chronic stimulation by RNA, may also lead to chronic inflammation and autoimmune diseases. This highlights the importance of targeting TLR3, as shown by data from TLR3 knock-out mice. Innate has developed humanized candidate mAbs that target TLR3. Data was presented at the 2013 Molecular Pattern Recognition Receptors Meeting showing efficient blocking of TLR3-induced signaling when the receptor is stimulated with two viral mimics, the synthetic double-stranded RNAs poly(A:U) and poly(I:C). Using these agents, Innate monitored activation of TLR3 in both peripheral blood mononuclear cells (PBMCs) and normal human broncho-epithelial cells. Using interferon-gamma induced protein (IP-10) or interleukin-6 (IL-6) as a readout of TLR3 activation, a dose-dependent reduction in IP-10 was observed for PBMC’s and a dose-dependent reduction in IP-10 and IL-6 was observed in normal human broncho-epithelial cells as shown in Figure 1.

Data were also presented that demonstrated efficient blocking of TLR3 signaling in mice using a surrogate mouse mAb. A reduction of signaling was observed both in vitro and in vivo using poly (A:U). Mouse models for both chronic obstructive pulmonary disease and colitis were also tested with the mAb, and significant improvements in certain metrics were observed in both models compared to approved anti-inflammatory drugs. The company is currently selecting a lead candidate to advance into regulatory preclinical development.

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On April 10, 2013, DelMar Pharmaceuticals (OTC BB: DMPI) presented clinical data at the 2013 AACR Annual Meeting from a Phase I/II clinical trial of VAL-083, a first-in-class chemotherapy for the treatment of glioblastoma multiforme (GBM). The new data demonstrates that VAL-083 is safe and well tolerated at the doses tested to date and there was an initial efficacy signal.

VAL-083 Phase I/II Dose Escalating Study.DelMar initiated a Phase I/II clinical trial of VAL-083 in November 2011. The study is an open label, single-arm, safety, tolerability and pharmacokinetic study of VAL-083 for adult patients with recurrent malignant glioma or secondary brain tumors that have failed both Temodar® (temozolomide) and Avastin® (bevacizumab), unless contraindicated. The trial protocol calls for administration of VAL-083 on the first 3 out of every 21 days.

The primary endpoint for the Phase I/II trial is to establish the maximum tolerated dose (MTD) of VAL-083. Secondary endpoints include monitoring antitumor activity, progression free survival (PFS), and pharmacokinetics of the treatment. Once the MTD is established, additional patients will be enrolled to begin the Phase II portion of the study and PFS will be monitored as the primary endpoint. 3 of 9 patients in the trial experienced a response, defined as either stable disease (2) or partial response (1), giving an initial indication of efficacy. While these are early results, an initial indication of efficacy before the MTD is reached is a promising sign.

VAL-083 is a bi-functional DNA alkylating agent with a long history of pre-clinical and clinical studies by the National Cancer Institute demonstrating its chemotherapeutic properties. It is currently approved in China for the treatment of chronic myelogenous leukemia and lung cancer.

On April 10, 2013, DelMar Pharmaceuticals (OTC BB: DMPI) presented clinical data at the 2013 AACR Annual Meeting from a Phase I/II clinical trial of VAL-083, a first-in-class chemotherapy for the treatment of glioblastoma multiforme (GBM). The new data demonstrates that VAL-083 is safe and well tolerated at the doses tested to date and there was an initial efficacy signal.

VAL-083 Phase I/II Dose Escalating Study.DelMar initiated a Phase I/II clinical trial of VAL-083 in November 2011. The study is an open label, single-arm, safety, tolerability and pharmacokinetic study of VAL-083 for adult patients with recurrent malignant glioma or secondary brain tumors that have failed both Temodar® (temozolomide) and Avastin® (bevacizumab), unless contraindicated. The trial protocol calls for administration of VAL-083 on the first 3 out of every 21 days.

The primary endpoint for the Phase I/II trial is to establish the maximum tolerated dose (MTD) of VAL-083. Secondary endpoints include monitoring antitumor activity, progression free survival (PFS), and pharmacokinetics of the treatment. Once the MTD is established, additional patients will be enrolled to begin the Phase II portion of the study and PFS will be monitored as the primary endpoint. 3 of 9 patients in the trial experienced a response, defined as either stable disease (2) or partial response (1), giving an initial indication of efficacy. While these are early results, an initial indication of efficacy before the MTD is reached is a promising sign.

VAL-083 is a bi-functional DNA alkylating agent with a long history of pre-clinical and clinical studies by the National Cancer Institute demonstrating its chemotherapeutic properties. It is currently approved in China for the treatment of chronic myelogenous leukemia and lung cancer.

VAL-083 Produced No Serious Adverse Events and Favorable Pharmacokinetics. Interim data was announced from nine patients receiving VAL-083 in the Phase I/II study. The patients were treated in three cohorts, each receiving a different concentration of VAL-083. The trial uses a standard 3 x 3 dose escalation design.[1] As part of this protocol, the first cohort is receiving 1.5 mg/m², the second cohort is receiving 3 mg/m², and the third cohort is receiving 5 mg/m² of VAL-083. Doses are administered on days 1, 2, and 3 of each 21-day cycle. Dose-limiting toxicity was not reached using these doses, and future patients will receive higher doses of VAL-083 until the maximum tolerated dose (MTD) or maximum specified dose is reached. Current patients have received anywhere from one to fifteen cycles of VAL-083 treatment.

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