In my previous article, published on Dec. 12th, 2013, I reviewed the company`s technology and development. Below I present an update on recent data and events of BIND Therapeutics Inc (NASDAQ:BIND). As a PhD in the biochemistry field I believe that BIND, with her nanomedicine platform represents the next stage in the evolution of targeted therapies and nanomedicine.
BIND Therapeutics, which was founded in May of 2006 and went public in September 2013, is a clinical-stage company developing polymeric nanopracticles. These nanopracticles, i.e. Accurins™ is designed to target specific cells or tissues at three levels: tissue, cellular and molecular. Accurins™ have the potential to significantly improve efficacy and safety, which is currently not achievable through other therapeutic approaches. This improvement according to the new data could provide a new "life" to old drugs. Given that the new trend in the drug industry is the combination of drugs, this Accurins™ could replace the old docetaxel mono-treatment for example, and enhance the effect of the combination of docetaxel with other drugs.
In my recent article I reviewed the company`s pipeline. It includes two types of programs: (1) proprietary and (2) collaboration (see Fig below). BIND`s current development focus is mainly in oncology, with its leading drug candidate BIND-014 in phase-II clinical trials for non-small cell lung cancer (NSCLC) and metastatic castrate-resistant prostate cancer (mCRPC).
BIND`s programs and pipeline
BIND is collaborating with leading pharmaceutical partners (Amgen, Pfizer, and AstraZeneca) to develop Accurins™ in line with each of their prospective products. The company stands to receive up to a total of $1 billion in upfront and milestone payments, including $450 million in pre-commercial payments. BIND expects that at least one of these collaborations will advance into the clinical Phase I by the end of 2014. Below are the specifics for each of the collaborations and their potential.
In April 2013 BIND and AstraZeneca (NYSE:AZN) entered into a strategic collaboration to develop and commercialize an Accurins™. At the Jefferies 2014 Global Healthcare Conference oral presentation Mr. Scott Minick, BIND's President and CEO, stated that the results show enhanced efficacy and increased tolerability. According to the results, the Accurins™ with Aurora B kinase inhibitor, showed reduce toxicity and increase efficacy as compared to AstraZeneca's parent drug. Importantly, it was able to significantly reduce the severe bone marrow toxicity seen in this entire class of drugs to a level similar to untreated controls. Under the agreement, AstraZeneca is required to pay for all of BIND`s development costs. BIND was paid $4 million upfront and has the potential to receive contingent future payments totaling up to $193 millions upon AstraZeneca`s achievement of specified clinical, regulatory and commercial events, as well as tiered royalties in the low-single digit to the low-double digit percentages of aggregate worldwide net sales of licensed product.
In January 2013 BIND and Amgen (NASDAQ:AMGN) established the first major partnership focusing on the development of a novel and targeted kinase inhibitor nanomedicine. Kinase inhibitor in Accurin™ has the potential to treat cancer more efficiently. BIND granted Amgen an option to obtain an exclusive worldwide license to develop, manufacture and commercialize an Accurins™ that incorporates a specified Amgen kinase inhibitor for all uses except for some vaccine applications. On December 12th, 2013 BIND announced that it has amended its development and commercialization collaboration agreement with Amgen Inc. to extend the period during which Amgen may exercise its option by six months. The additional period under the amended collaboration agreement was extended to July 7, 2014 in order to allow for completion of the research plan. BIND has already received $5 millions upfront. BIND is eligible to receive upfront development milestone payments totaling $46.5 millions, up to an additional $134 millions in regulatory and sales milestone payments for the first therapeutic indication and additional payments for target exclusivity. In addition, BIND will receive tiered royalties on potential future sales.
Why I believe Amgen will exercise its option:
At the Jefferies 2014 Global Healthcare Conference an interesting result was presented: The use of an inhibitor of the phosphoinositol-3-kinase (PI3K) pathway, which is part of Amgen`s development, in conjunction with the Accurin™ led to a reduction in the toxicity. PI3K is the hottest inhibitor in cancer research to date. It plays a crucial rule in the cancer development; therefore, inhibiting this pathway already achieved great results. The only problem with these inhibitors is their toxicity. BIND-014 shows promising results in reducing the toxicity, thus becoming an important player in this field. In addition, Amgen waited to a proof of concept that the kinase inhibitor with the Accurin™ can reduce toxicity and increase efficacy relative to the parent drug. Taking AstraZeneca results and the new Amgen result, I think that Amgen will not let this development slip from their fingers; therefore, they have time until July 7 to close the deal.
In March 2013 BIND and Pfizer (NYSE:PFE) entered into a global collaborative agreement to develop and commercialize Accurins™ utilizing selected small-molecule targeted therapies. BIND granted Pfizer a 30-month option to exclusively license Accurin™ for all potential indications other than vaccines and brain cancer. Under the agreement, Pfizer is required to pay for all of BIND`s development costs. BIND received an upfront payment of $4.0 millions and may potentially receive contingent payments totaling up to $89.5 millions in clinical and regulatory milestones, plus additional contingent payments totaling up to $110 millions in specified commercial milestone payments. BIND will also receive royalties in the low-single digit to the high-single digit percentages of aggregate worldwide net sales of any licensed product. This would also represent a substantial cash influx into BIND.
Update on BIND-014
BIND-014 is a prostate specific membrane antigen with PSMA targeting Accurin™ that contains docetaxel, one of the most widely used cancer chemotherapy agents. PSMA is a cell surface protein expressed on prostate cancer cells and the abnormal blood vessels surrounding many types of non-prostate solid tumors, including non-small cell lung cancer. BIND-014 is currently in Phase II clinical development for second line non-small cell lung cancer in chemotherapy naïve metastatic castrate resistant prostate cancer. BIND expects to report the top line data on this trial, as well as Phase II trial in chemotherapy naïve metastatic castrate resistant prostate cancer in the second half of this year.
At the AACR 2014 Annual Meeting and in the Jefferies 2014 Global Healthcare Conference oral presentation, BIND presented new data supporting its technology. In a poster presentation entitled "A phase I study of BIND-014, a PSMA-targeted nanoparticle containing docetaxel, administered to patients with refractory solid tumors on a weekly schedule," phase I data were demonstrated on safety, pharmacokinetics and preliminary efficacy of BIND-014 administered as a 60-minute infusion once weekly for three weeks (Q1W), followed by one week without treatment over a four-week cycle. Greater dose intensity by approximately 50% was shown with Q1W dosing of BIND-014 as compared to once every three week dosing. Different tolerability profiles were demonstrated with BIND-014 dosed at Q3W and Q1W. The Q1W schedule demonstrated considerably less neutropenia than Q3W BIND-014, a major dose-limiting toxicity for docetaxel, even at the higher dose intensity. Pharmacokinetics of BIND-014 was consistent with prolonged retention of BIND-014 particles in the vascular compartment and controlled release of docetaxel at the tumor. The results also showed preliminary signals of antitumor activity on the Q1W schedule. These results show that BIND-014 delivers the payload to the cancer.
In another poster presentation at the AACR 2014 Annual Meeting, entitled "Prostate-specific membrane antigen (PSMA) expression as a potential patient selection marker in patients with refractory solid tumors administered BIND-014, a PSMA-targeted nanoparticle containing docetaxel" it was shown that the PSMA expression in patients responds to the treatment with BIND-014 in the phase I clinical study. A positive PSMA expression of moderate or high intensity was observed in patients who demonstrated a response to BIND-014 in the phase I study. Preferential expression of PSMA was observed on prostate cancer cells and vasculature of non-prostate solid tumors, but not in normal (non-cancerous) vasculature. PSMA expression levels will be evaluated in the tumors of patients enrolled in phase II clinical studies with BIND-014 to investigate the correlation between expression and efficacy as a potential basis for patient selection.
Looking at the results so far, and looking at other delivery programs of different companies (for example; CytRx Corporation (NASDAQ:CYTR)), I estimate a 70% chance for these phase II to achieve its end point.
Promising activity in NSCLC patients with KRAS mutant tumors
The KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene is involved in regulating cell division and belongs to a class of genes known as oncogenes, which when mutated, have the potential to cause normal cells to become cancerous. The Non-small cell lung cancer patients with KRAS mutations have high unmet need with lack of approved therapy and a poor prognosis. These patient populations typically do not respond to docetaxel treatment. As to the ongoing NSCLC phase II trial, in the Jefferies 2014 Global Healthcare Conference oral presentation it was shown that in KRAS mutant of NSCLC had a partial response, as good as 60% change in targeted lesions from baseline. These results led to the preparation of a 20 patients with KRAS mutations phase II trial that will start in early Q3 2014. This data is encouraging given the lack of approved therapeutics in this population and the apparent differentiation from conventional docetaxel.
BIND also plans to start in Q4 another trial in four tumor types, cervical, bladder, cholangio and neuroendocrine cancer. These trials will enroll approximately 25 patients in each tumor type to evaluate efficacy. There is a significant unmet medical need in each of these tumor types and three of them represent a potential opportunity for accelerated approval due to unmet medical needs and available approved therapies.
Company Financial Position
The cash equivalents and marketable securities were $68.7 millions as of March 31st, 2014. Net loss for the first quarter of 2014 was $8.3 millions. According to these financial data, BIND has enough cash to fund operations through 2015, even without any additional contributed amount from Amgen, Pfizer or AstraZeneca, which is always a great advantage and a strong financial position for a developmental biotechnology company.
There is no investment without a risk attached to it: The main risk is that the expected results forecasts might not be met. Nevertheless, there is no success without taking chances. Another possible risk facing investors is a dilution concern. Yet, I do not expect to see a dilution until 2015 and if Amgen and Pfizer decide to exercise their options bind will get a substantial cash of money and will not have to make dilution in the very near future.
Summary and conclusion
Current fundamentals indicators, demonstrate that BIND could potentially become the next promising and unique company in the oncology field. The new data given in number of conferences further show that Accurins™ is an efficient and safe delivery system. Investors should look towards the decision of Amgen and/or Pfizer to exercise their option with BIND. Time is closing in as Amgen has until July 7, 2014 to make its move and decide. Due to new results, who were brought in this article, I believe that there is an excellent chance that Amgen will exercise their option with BIND. If Amgen exercises its option, BIND is eligible to receive upfront development milestone payments totaling $46.5 millions and additional $134 millions in regulatory and sales milestone payments.
Investors should also look towards rapid advancement of BIND's leading drug candidate, BIND-014, in Phase II clinical trials for non-small-cell lung cancer (NSCLC) and metastatic castrate-resistant prostate cancer (mCRPC) with topline data in the second half of this year. I estimate a 70% chance of success in the two phases II trials in NSCLC and prostate cancer. I base my opinion on my research of companies with delivery systems. Next on the horizon for BIND in 2014 is the initiation of a single arm open label 20 patient trials in non-small cell lung cancer patients with KRAS mutations, which should begin enrolling patients in early Q3 and additional tumor types in which there is strong biologic rationale for BIND-014 treatment including cervical, bladder, cholangio and neuroendocrine cancer in Q4.
I believe that BIND is undervalued at its present market capitalization of around $135 million and with approximately $68 million in cash. Analyst covering BIND gave price target between 20$ - 30$:
Stifel Nicolaus - 20$ target price.
BIND)+at+Outperform/8776012.html" target="_blank" rel="nofollow">Cowen & Co. - 30$ target price.
JMP Securities - 30$ target price.
Credit Suisse - 21$ target price.
I reaffirm my estimated price target of $20 excluding Amgen`s or Pfizer`s potential to exercise their options. This price target is based on the assumption that the phase II trials will be successful. In case Amgen and Pfizer decide to exercise their options, the likelihood of BIND to triple its value and reach a price target of $30 by the end of 2014 is highly plausible, since BIND stands to receive up to a total of $1 billion in upfront and milestone.
Disclosure: I am long BIND. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.