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Sanofi Edges Ahead in Diabetes Race, Announces Yet Another Regeneron Potential Blockbuster

By
Jennifer Aldershot
-
Sanofi

On July 29, 2015, Sanofi (NYSE:SNY) announced that it had met the primary endpoint in its phase 3 study of LixiLan, a combination treatment targeting diabetes that combines lixisenatide with the company’s current top-selling insulin product Lantus. Just a day later, the company announced that it was entering into an immuno-oncology collaboration with Regeneron Pharmaceuticals, Inc. (NASDAQ:REGN) – hot off the heels of the FDA announcement that it was approving the Sanofi/Regeneron PCSK9 inhibitor, Praluent, targeting high cholesterol – an approval that sees the treatment become the first PCSK9 inhibitor to gain approval in the US. Further, on the same day, Sanofi reported its Q2 2015 financials. In other words, it has been a pretty big week for Sanofi, and one that warrants address. So, with this said, let’s look at each of these developments individually, and try to ascertain where they fit into the bigger picture for the company.

So, first, LixiLan. As we said, the treatment is a combination of the company’s current  insulin product Lantus and a glucagon-like peptide 1 receptor agonist (GLP-1 RA) called lixisenatide. GLP-1 is a hormone released after humans eat meals, which suppresses glucagon secretion and stimulates insulin production. As an agonist, GLP-1 RA increases the production of GLP-1 and, as the latest trial results have shown, can work in tandem with a traditional insulin treatment to improve efficacy. The company had to phase 3 trials running, one that trailed the combination therapy in 1170 patients and a second that is ongoing, and studies the treatment in a further 736 patients. The primary endpoint of a statistically superior reduction in average blood glucose over the previous three months, when compared with the two components of the combination therapy used solo, came in as met in the initial 1170 patient trial. The second trial will complete during Q3, 2015. So what are we looking at from a timeframe perspective as far as getting approval and benefiting from any resulting upside market revaluation in Sanofi? Well, the company expects regulatory submission during Q4 this year in the United States and Q1 next year in the EU. Tack about six months on to each of those prospective timeframes, and we will be looking at approval somewhere midyear 2016 in the US and end of year 2016 in Europe. Worth noting are a couple of competing treatments, one of which is Novo Nordisk’s (NYSE:NVO) already European approved GLP-1 in combination with its current insulin treatment Tresiba (making a second attempt at approval after a 2013 rejection by the FDA) and Eli Lilly and Company’s (NYSE:LLY) Trulicity. In short, the next 12 months, this is likely to be a real hot space in biotech.

So, now to the company’s fresh partnership with Regeneron. The announcement highlighted a new collaboration between the two companies that will see them partner up on protein inhibitor REGN2810, currently in phase 1 trials. Sanofi will pay $640 million upfront, with a total of $1 billion invested in combination from the two companies ($750 million of which will come from Sanofi) for discovery through proof of concept studies on alternative monotherapy antibody candidates. Exactly what these candidates will be at the moment is pretty uncertain, as neither have specified in their announcement, but we will likely be looking at antibodies that work in collaboration with the current (and aforementioned) PD-1 inhibitor REGN2810. Conservative forecasts put the immune-oncology space at $10 billion annually over the next five years, and the latest play by Sanofi and Regeneron looks to position the two companies to take advantage of this growth.

Jumping ahead to the company’s current financial position, Sanofi reported €9.4 billion in sales during the second quarter of 2015, a 4.9% increase when accounting for constant exchange rates. The well profiled diabetes area of its current operations was expected to reduce, and did just that, coming in at a 3.8% decline on the quarter, but without this expected decline, total group sales came in at 7.3% higher quarter over quarter.

So, what’s the takeaway here? Well, it looks as though Sanofi is going all in immuno-oncology. As mentioned, the space is set to explode over the next five years, and if the Regeneron partnership bears fruit, both companies will be well-positioned to direct a proportion of the $10 billion sector valuation towards their own balance sheets. From a diabetes perspective, things are a little less clear, but the latest announcement keeps Sanofi in the running of a highly competitive race between itself, Eli and Novo.

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Progenics Pharma Soars, Here’s Why

By
ME Staff
-
Progenics Pharma

An hour before market open in the US on Tuesday, Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX) announced that one of its candidates had received US Food and Drug Administration (“FDA”) breakthrough therapy designation. The company’s market capitalization gained a little over 22% during the first part of the US session, before settling to close around $9.42 – giving back some of the gains but still 4% up on the previous day’s close. We have had a number of key announcements from the Progenics over the last few weeks, and the latest is just one in a series of potential market movers for the company. However, with this said, and now the breakthrough designation is in place, is there likely any further short to medium-term upside potential in the company’s stock, or is it worth waiting a little longer before gaining exposure to a revaluation? To answer, let’s have a look at the treatment in question, and a couple of the previous announcements with regards to how they relate to Progenics’s near term prospects.

So, first, let’s get to the science. The treatment in question is called Azedra. Azedra is a late stage drug candidate in development for the treatment of malignant pheochromocytoma and paraganglioma – which are essentially very rare brain tumors that develop from cells in the sympathetic nervous system. Basically, the human autonomic nervous system is split into two parts – the parasympathetic nervous system and the sympathetic system. The sympathetic nervous system is responsible for what we refer to in the nonscientific world as the fight or flight response, and as you might have guessed, includes the adrenal glands. A malignant pheochromocytoma is a tumor that forms in the sympathetic nervous system but is not attached to adrenal glands. Conversely, a paraganglioma is a tumor that attaches itself to adrenal glands. So, with this out of the way, what is the difference between this and current standard of care treatment? Well, it all comes down to targeting. Azedra is a small molecule (just another term for the type of molecule that makes up most drug treatments) with a radioisotope attached to it. When introduced to the body, it can first be used as an imaging agent as the combination of the small molecule and radioisotope targets both pheochromocytoma and paraganglioma highly specifically, and then once identified, can be channeled to deliver specific and individualized radio treatment to the tumors. Current standard of care is pretty hit and miss, and includes an adrenergic blockade (which has obvious negative side-effects) surgery, which is risky in the sympathetic nervous system, and chemotherapy, which has generally been shown to fail to produce a cure or generate significant remission.

So why the upside momentum from the breakthrough designation? Well, the treatment is currently under evaluation in a pivotal Phase 2b trial, and already has orphan drug and fast-track designation is from the FDA, since it is designed to treat a very rare indication. Breakthrough designation means that Progenics can hold regular meetings with the FDA throughout the drug development in order to gain real-time insight into how best to do things such as trial design, in order to achieve approval. There is also a cross-disciplinary review panel, which again, from an advisory perspective, can increase the likelihood of approval (of course, so long as efficacy is shown). Fast-track designation is very similar, in that it offers more frequent FDA interaction and the potential for rolling review, meaning the FDA will review each stage of the drug’s development rather than wait until it is all complete a review it as a whole.

So, put simply, what does all this mean? Well, the current phase 2 trial is a pivotal trial, meaning that – if it is successful – Progenics may be able to get approval for Azedra without having to conduct the usual phase 3. The trial started in late 2010, but was suspended whilst the company sought additional funding. Reenrollment began again in January this year, and at that point, the company treated 41 patients with 30% of them achieving the primary endpoint. In order to be considered for approval, 25% of the total of 58 evaluable patients must achieve the similar endpoints.

So what sort of timeframes are we looking at? Well, the company expects to complete the main part of the trial before the end of this year, or at least expects to complete enrolment before this year closes out, and so we could be looking at second half 2016 before we get trial end data. However, as things develop, interim data has the potential to move the stock on positive news. So, to answer the initial question, will we see further upside momentum between now and trial completion? In all likelihood, yes. Providing, the drug can maintain its current performance as Progenics seeks to treat the remaining portion of its required subject panel.

Looking for other breakthrough designation approval plays? Check out Dyax Corp. (NASDAQ:DYAX), Ariad Pharmaceuticals, Inc. (NASDAQ:ARIA) and Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN).

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What Allergan’s “Big Week” Really Means for its Future

By
Jennifer Aldershot
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Allergan

This week has been a big week for Allergan (NYSE:AGN). First, we heard that the company was selling its generic drug company to Israel based Teva Pharmaceutical Industries Ltd (ADR) (NYSE:TEVA). The deal, worth a reported $40.5 billion, is the largest ever acquisition by an Israeli company, and comes at a time when many are betting against the biotech space on the pretense we are approaching the end of a five year bubble. Almost as soon as we got the Teva news, however, we got a follow up announcement that Allergan is set to acquire Illinois based Naurex Inc. for a flat $560 million. The two deals are the latest in a string of high profile acquisitions in the biotech space, and Allergan is up more than 6% on the week’s open. With this said, is there further upside potential in the company’s stock, or are the gains we have seen the entire short-term market response, and must we wait for the fruits of the acquisitions before we see any further considerable action. In order to answer, lets take a look at the terms of both deals, and try to ascertain the medium term impact of each on Allergan’s market capitalization.

First, lets look at the Teva deal. As we have mentioned, the deal will see Teva take on the entirety of Allergan’s generic pharmaceuticals business for $40.5 billion. Teva is already the largest generic pharmaceutical company in the world, and the latest acquisition cements its positioning in the space. One of the primary drivers behind the acquisition, it seems, is an increased amount of pressure being put on Teva Chief Executive Erez Vigodman by shareholders to expand the company’s revenue sources, from a diversification perspective. Approximately 48% of the company’s profits currently come from multiple sclerosis drug called Copaxone, and with a number of other multiple sclerosis trials hitting headlines recently in the non-generic world, the necessity for diversification has been pressing issue. Teva ‘s stock is up nearly 20% on the announcement, in part due to this diversification, but also as a result of the cost savings likely to come about as a direct benefit from the acquisition. Not only will Teva be able to reduce operational costs through economies of scale, but also the increased generic portfolio will give it a higher leveraged rate when it comes to negotiating with healthcare organizations and – in particular – US insurance companies. This increase leveraged should improve the company’s bottom line very quickly upon acquisition completion.

So now moving on to the second deal, the $560 million acquisition of Naurex Inc. by Allergan. The acquisition strengthens Allergan’s development pipeline, bringing two potential blockbuster treatments under its umbrella. The first is an intravenous depression treatment that has already proved efficacy in phase 2 trials and is heading into phase 3 before the end of this year, and an oral treatment for the same indication that has demonstrated promising results in early stage testing. Both are demonstrated tolerability, and bring a novel approach to depression treatment by targeting the receptors in the brain responsible for memory, that also contribute to glutamate levels (which, research shows, are out of sync in depression patients). Is a quick side note, it’s worth mentioning that the deal is not set to close before the end of 2015, but its value could rise from an Allergan perspective as there are a number of milestone payments due based on the research sales success of the aforementioned pipeline candidates.

So how should we approach these two deals, and where do we expect Allergan to head going forward? In short, we should look at them as very much part of the same development plan. Allergan has stated that it wants to reduce its debt (somewhere around $44 billion at the moment) to 3.5 times adjusted earnings by the end of this year. The company is also stated that it wanted to abandon the generic industry in order to focus on more targeted developed stage treatments. The Teva deal allows the company to reduce its debt holdings, while also freeing up capital to expand into the development side of things; indeed, Chief Executive Brent Saunders has stated that the company will use around $36 billion in net proceeds from the sale to fund further large acquisitions.

So in other words, Allergan has cashed in on its generic business at what seems to be an excellent price, and aims to use the vast majority of the proceeds to buy up developing stage pipelines. This is a switch in strategy for the company, but one that could prove very profitable in the long-term. With a $36 billion blank cheque, there are a number of attractive pipelines the company could go after, with rumors suggesting that Biogen Inc (NASDAQ:BIIB), Amgen Inc. (NASDAQ:AMGN) and AbbVie Inc. (NYSE:ABBV) as potential targets. Each of these companies has at least one potential blockbuster in its pipeline, and as such, it may be worth picking up and exposure to Allergan before it becomes the biotech incumbents that a $45 billion payday gives it the potential to be.

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Could This Treatment Replace Morphine in the US?

By
Roger Hannington
-
Cara Therapeutics

When markets opened in the US on Monday morning, Cara Therapeutics Inc (NASDAQ:CARA) traded for a little over $15. Premarket on Thursday, and throughout Thursday’s session, we saw high-volume and a spike to intraday highs just shy of $22 flat. We closed the day around $19, and it looks as though we’re going to get further gains today. All said, after a 30% up spike, we settled on around 25% gains in a little over 24 hours. The gains were rooted in a press release put out by Cara therapeutics premarket on Thursday, offering a taste of its topline results from one of its currently pipeline candidates – CR845. Markets translated the results as overwhelmingly positive, and expect Cara to now take its candidate into a phase III pivotal trial. However, as always, phase II success far from guarantees FDA approval, and further to that, FDA approval far from guarantees marketing success. So, with this said, is the 30% gain warranted? In addition, should we expect further gains based on this latest result, or have short-term speculative biotech traders missed the boat? To answer, let’s take a look at the treatment itself, how it performed in the latest trial, and what we could be looking at from a market potential perspective if the treatment is successful in its planned phase III.

So, first, let’s address the science. As part of the latest trials, Cara tested CR845 inpatients suffering from uremic pruritus – a chronic itch condition associated with sufferers of end-stage renal disease. The condition manifests itself as a skin condition, and does not associate itself with any particular gender, age, ethnicity or root cause of renal failure – presenting Cara with a relatively wide subject base in its trial. The treatment is what we might call an alternative take on current opioid analgesics such as morphine and oxycodone. These aforementioned have a mechanism of action that allows them to activate fresh opioid receptors in the central nervous system, essentially tricking the brain into overlooking pain signals from a particular area of the body. CR845, on the other hand, is a periphery treatment – in that it binds to opioid receptors at a specific target, but does not enter the central nervous system. For this reason, it does not affect the brain in the same way that traditional opioid analgesics do, which translates to a similar efficacy with a huge reduction in adverse effects. In the US, opioid analgesic abuse has reached epidemic levels, and Cara therapeutics believes periphery opioid analgesics such as CR845 can overcome this epidemic. Sounds interesting, right? Essentially, you can think of it as nonaddictive morphine.

So how did it perform in trials? Well, as we said in the introduction, we only have a taste of the topline results so far. However, this is enough to suggest a phase 3 pivotal could well be just round the corner. In the double-blind, randomized, placebo-controlled trial we saw a 54% greater reduction in worst itch sores for patients treated with CR845 than those receiving placebo – in other words, primary endpoint met. From a secondary endpoint perspective, the company allocated what’s called a Skindex score to patients receiving the treatment, which is essentially a baseline measure of improvement in dermatological conditions. In the trial, those treated with the drug experienced a 71% greater reduction in average total Skindex score over a two-week treatment period than those receiving placebo (for reference, a reduction is positive when it comes to Skindex). Finally, CR845 came out safe, well tolerated and did not demonstrate any serious adverse events. The only real side-effects were transient numbness (essentially numbness at point of injection) and a little bit of dizziness. Most importantly, there were no central nervous system associated side-effects, which had been the scourge of central acting opioid analgesics in the past.

So what is the market potential? This is a first in class treatment, meaning that we have very little to compare it to when it comes to price point. However, from a volume perspective, if Cara Therapeutics can achieve approval for CR845 it would be able to price the drug relatively cheaply and still generate significant revenues from its delivery. There are approximately 400,000 people in the US that suffer from renal disease, with about 50% of these experiencing uremic pruritus. On a global scale, we are looking at 2.2 million renal disease sufferers with, once again, about a 50% incidence rate of uremic pruritus.

So what’s the takeaway here? Well, Cara expects to initiate a phase III trial early next year, and if results mimic those with seen in the recent phase II, this treatment has the potential to be a real blockbuster for the company. The gains look valid, therefore, but from a big picture perspective, they look to be just a drop in the ocean of what could potentially be a game changing treatment. As mentioned, opioid analgesic addiction is a real problem in the US and globally, and if Cara can demonstrate efficacy and marketability for CR845 we could see the treatment start to replace morphine in a wide range of indications. In other words, longer-term, this could be a real winner. Cara is not quite in the league of its pharma mega cap counterparts such as Pfizer Inc. (NYSE:PFE) and GlaxoSmithKline plc (ADR) (NYSE:GSK), but a winner like this has the potential to elevate it a step closer.

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What Is the Real Cost of AstraZeneca’s Eye Cancer Flop?

By
ME Staff
-
Astrazeneca

On July 22, 2015, we learned that AstraZeneca’s (NYSE:AZN) oncology candidate selumetinib had disappointed in a recent phase III trial. The news hit markets overnight on Tuesday, and as a result, pre-session trading put pressure on AstraZeneca’s stock, and we are now trading above 2% down from the levels we were looking at pre-announcement. The value of the treatment itself is obviously a setback for the company, but it is a wider perception of AstraZeneca’s current standing and outlook that markets will take heading forward. Just last year, CEO Pascal Soriot walked away from a $120 billion takeover from rival incumbent Pfizer (NYSE:PFE), pledging that he would raise revenues by 75% between then and 2024 – targets that, at the time, analysts suggested as leaving the company very little room for error over the succeeding decade. AstraZeneca is currently trading about 20% lower than it was when the takeover was on the table, and about 30% lower than the premium price at which Pfizer was willing to pick up outstanding shares as part of the deal. It goes without saying, therefore, that the latest announcement puts considerable pressure on Soriot from a shareholder perspective. However, the question is, is the selumetinib absorbable in terms of staying on progress for a 75% ten-year revenue expansion, or has it derailed this prospect? To answer, let’s take a look at the treatment, how it fared in the recent phase III, the revenues AstraZeneca stands to miss out on as a result of the failure, and finally, whether or not it can claw back any of these revenues on alternate indications for the treatment.

First, let’s address the science. Selumetinib blocks an enzyme called MAPK kinase, which is an integral part of the MAPK pathway – a chain of proteins that communicates and processes input from a range of growth factors in a cell. In cancerous patients, this communication can activate a mutation in a gene called BRAF, and can lead to further mutations and proliferation of cancer cells. By blocking the MEK1 and MEK2 subtypes of the MAPK kinase gene, selumetinib (hypothetically) can be put to use treating a range of cancers – and in this instance – uveal melanoma, a cancer that causes tumor cells to grow in ocular tissue and has an incidence rate of about 2000 in the US annually. The company did not report specific figures as far as trial data is concerned, but instead chose to simply announce that the phase 3 study of selumetinib in combination with dacarbazine (an older, standard of care treatment) failed to reach its primary endpoint of progression free survival. The results also showed an unreported adverse event profile compared with the aforementioned standard of care. It’s worth mentioning that markets reacted particularly negatively to the release, as mid stage data suggested blockbuster results and had AstraZeneca investors poised for a quick approval.

So what sort of revenues were we looking at four AstraZeneca if the company succeeded in phase III and achieved approval? Well, as mentioned, the incidence rate for this treatment is relatively small. However, the cost for current treatment options is high. The two standard of care treatments are either radiation therapy or surgery to remove the eye altogether. Since we are looking at treatment rather than removal, it is reasonable to compare the former with selumetinib rather than the latter. The two types of radiation therapy available are what are called brachytherapy and proton beam therapy, which according to a National Cancer Institute study that compared the treatment on a base case incremental cost effective ratio with a enucleation (complete removal), come in at $77,500 and $106,100 respectively. While it is unrealistic to suggest that AstraZeneca could have achieved high percentage saturation within 3 to 5 years, low double-digit market share is not unreasonable. At a conservative cost of $50,000 per treatment, selumetinib could very easily have become a mid double-digit million dollar candidate for the company.

All this aside, AstraZeneca continues to develop the treatment for a number of different indications, including thyroid cancer and non-small cell lung cancer. With these further indications, analysts put 2020 sales at a little over $305 million. This, of course, is assuming we don’t get a turnaround in fortunes as we have seen with the ocular indication.

So what’s the takeaway here? Using some rough calculations, it looks as though the recent failure stands to cost AstraZeneca at least $40 or $50 million in forsaken revenues – approximately 18% of its total forecast for selumetinib revenues in 2020. However, it’s not by any stretch of the imagination a fatal blow for the company’s projections. With a number of larger incidence rate target cancer treatments in the pipeline, including AZD9291, Lynparza and MEDI4736 – all of which could be billion-dollar blockbusters if approved – the company is still on track for its 75%, decade long revenue increase. Long term on track, yes, but temporarily derailed – undoubtedly.

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Phase III Success Makes this Company a Potential Blockbuster Biotech

By
ME Staff
-
Exelixis

It’s been a big week in biotech. First we had the announcement that DBV Technologies (NASDAQ:DBVT) was all set for a follow-up financing round in which it expects to raise more than $240 million to fund phase III of its peanut allergy treatment. Then we heard that Tekmira Pharmaceuticals Corp (NASDAQ:TKMR) is set to change its name to Arbutus Biopharma Corporation under the ticker “ABUS” to fall in line with a new focus on Hepatitis B. Now, as markets kick off for a fresh day in the US, we have got yet another piece of big news out of the biotech space, namely that oncology junior Exelixis, Inc. (NASDAQ:EXEL) has finally achieved some level of success with its renal cell carcinoma candidate cabozantinib. Those of you following this company will remember the treatment’s phase III failure in a prostate cancer indication last September, and the ensuing turmoil that surrounded Exelixis as a result. Within hours of the failure announcement, the company’s market capitalization halved, and Exelixis slashed 70% of its workforce before the beginning of 2015.

Sellers at that time can be forgiven for wanting to get out of what looked like a Jr biotech in real trouble – something that, if held onto for an extended period of time – can wipe out an exposure. However, for the more risk tolerant participants that held on to their Exelixis allocation, there is finally some reprieve. On July 20, 2015, the company announced that – in a trial that compared cabozantinib to everolimus (current SoC) – the treatment reduced the risk of disease progression or death by 42% across a sample size of 658 patients with metastatic renal cell carcinoma (kidney cancer that has spread beyond the kidneys). Reduction of progression or death risk was the primary endpoint, meaning the trial passed with flying colors. At time of writing, Exelixis is up more than 50%, and looks likely to close out today even higher.

So why all the action? Well, the recent announcement has brought the company to trade at fresh yearly highs, breaking resistance from mid-2014 of around $4.5, and with what looks like it could be a fast-track route to approval there will likely be further upside revaluation throughout the latter half of 2015 and as we head into the beginning of next year.

So let’s take a quick look at the treatment and the science from which it derives its method of action. Cabozantinib is what is called a tyrosine-kinase inhibitor (“TKI”) – which, as its name suggests, is an agent that inhibits tyrosine kinases. These are the enzymes that are responsible for protein activation that can lead to proliferation in cells, and therefore, can be responsible for metastasis, growth and reproduction of cancerous cells. By inhibiting tyrosine kinases, Exelixis hypothesizes that cabozantinib can reduce tumor size and – in turn – effectively treat cancer across a variety of indications.

So what sort of timeline are we looking at before we will likely see any approval? Well, the drug is one of a number of the FDA’s fast-track designations, meaning that, assuming the NDA filing takes place before the end of this year, we could be looking at an approval during the first quarter of 2016. The treatment is currently approved for a medullary thyroid cancer indication, however, there are only between 200 and 300 patients suffering from this indication in the US. If we get approval for the kidney cancer indication, this number will increase to nearly 20,000 potential patients. Therefore, it goes without saying, that this indication can be a potential blockbuster for the company. There is also a kidney cancer indication trial ongoing, with results expected 2017, and a combination trial using cobimetinib, another of the company’s pipeline candidates, and Zelboraf, an already approved treatment currently being marketed and manufactured by Roche (OTCMKTS:RHHBY). This, combination treatment could receive approval as early as November this year.

So, what’s the takeaway here? Well, that there is real potential in this stock. The company took a beating late last year, and its shares have been trading at what now look to be a deep discount ever since. Investors that got in at the base of this discount are already looking at a decent upside return, but the potential for further return exists. With approvals looking likely at both the end of this year and at the beginning of next, as well as phase III trial results expected during early 2017 for a second indication, now looks like a great time to get an exposure to any potential upside revaluation in this company going forward.

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Here’s What Markets are Asking About DBV’s Follow Up

By
ME Staff
-
NASDAQ

In October last year, DBV Technologies (NASDAQ:DBVT) hit the markets with a pretty disappointing IPO, closing out at an average of around $21 per share versus its pre-IPO target of a little over $23 a share. However, over the last eight or nine months, the company has really found its stride, and we are now trading around $42 a share – 85% up on its IPO pricing and a nice return for those that got in last October. Just this week, we learnt that the company is taking advantage of its current rosy market situation, and launching a follow-up share offering to fund – among other things – a phase 3 program for its lead candidate – Viaskin. The question now facing potential contributors to this follow-up offering is simple. With hindsight, a $21 a share offering presented a discounted opportunity to gain exposure to what would turn out to be one of the hottest development stage biotech’s of the last six months. However, with the stock now up nearly 85%, is an entry at this price still a discount on a long-term valuation? If the answer is yes, then the follow-up is worth taking part in. If no, it is best left alone until we actually see some progress from the trial that the company is looking to fund. So, with this said, let’s have a look at the offering itself, and attempt to come down on either side of the question.

So, first, let’s take a look at the drug the company is looking to fund. As we have said, the candidate is called Viaskin, and currently has two primary indications – peanut allergy and cow’s milk protein allergy (CMPA) in children. In both incidences, the treatment uses a patch that contains an allergen protein in its original antigenic state. When exposed to the skin, the allergen is exposed to the allergen protein over an extended period of time. This extended exposure translates to activation of regulatory T cells, which not only treat allergies during exposure, but also (due to the nature of the human immune system) for a period once exposure ceases. Because the allergen is delivered to what are called Langerhans cells, they avoid the bloodstream and – in turn – avoid systemic allergic reactions, something that can vastly improve the safety profile of the treatment and give it an advantage over current standard of care.

So where are we with trials? The vast majority of the funds will go towards advancing the former of these two indications – the peanut indication – into phase 3 trials. With this in mind, let’s focus on the peanut indication for the purposes of judging the company’s current position in the market.

In September last year, we learnt the topline results for a phase IIb trial of 221 peanut allergic subjects across four treatment arms (three variable and increasing dosage levels and one placebo). At the beginning of this year, we heard a full study report during the 2015 AAAAI Annual Meeting in Houston, Texas. The trial showed efficacy, with 50% reaching primary endpoints compared to 25% on the highest dose level across all responders, and further, 53% exhibiting efficacy versus 19% in the child focused arm of the trial, designed to study children ages six to 11. Further, and just as importantly, safety was confirmed, with no treatment-related adverse events reported.

Things look promising so far, so what are the terms of the offering? Well, the company is offering 3.6 million shares in the form of 7.2 million American depositary shares (ADS), with each ADS representing one half of one ordinary share. Estimated net proceeds come in at around $230 million, slated to a public offering price of $34 per ADS. As we have said, the vast majority of the proceeds will go towards the phase 3 trial, and it is this trial that could be the primary driver behind any upside revaluation in DBV stop going forward.

So what are the risks? Well, as usual, there is the risk of non completion of the trial. Some of this is mitigated by the upcoming financing round, but if we fail to see the efficacy seen in the phase IIb, progress could falter. We also have to consider competition, and potential market size/saturation. Interestingly, in this instance, not from a direct comparable treatment, but from current standard of care – EpiPen, manufactured by generic drug incumbent  Mylan NV (NASDAQ:MYL) in conjunction with King Pharmaceuticals, which since a recent takeover is now an arm of Pfizer Inc.(NYSE:PFE). Sales of the EpiPen reached $1 billion for the first time early this year. Obviously the EpiPen controls the market at present, and unlike the treatment offered by DBV is a responsive treatment rather than preventative, but with a current market cap of $1.5 billion, it is easy to see how an approval for the peanut indication, followed by a small grab of market share (low double digit percentage) could turn Viaskin into a hit for DBV. Further, this is only one indication – the potential going forward is even bigger.

So, with all this said, where do we stand on the follow-up offering? Well, simply put, it looks attractive. Yes, DBV is 85% up on its IPO price, but as we head into phase III trials, all and any news releases have the potential to drive volatility. Get on the right side of this volatility, and we could see another similar upside revaluation during the next 12 months.

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This Deal Suggests Biotech Is Far from Its Peak

By
ME Staff
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Receptos

The fact that global biotech markets could be in the late stages of a bubble that kicked off between four and five years ago is making some investors, both private and institutional, wary about allocating capital to the space. After a number of temporary corrections during which analysts suggested we may start to finally see a turnaround in the sector, we continue to trade higher and higher in the major biotech indices, outstripping the vast majority of other industries along the way. However, there are a number of companies that seem to remain extremely bullish on biotech prospects. One of these is Celgene Corporation (NASDAQ:CELG). How do we know? Through its spending and acquisition activity. Over the last few weeks, we’ve seen Celgene acquire Juno Therapeutics Inc. (NASDAQ:JUNO) at nearly twice its open market rate in a $1 billion deal, we’ve seen the company expand its deal with Epizyme, Inc. (NASDAQ: EPZM) in what, over time, could be a close to $650 million deal, and finally, a realignment of its partnership with bluebird bio, Inc. (NASDAQ: BLUE) to the tune of a reported $225 million per product. If an incumbent biotech like Celgene is taking twice open market rate positions on developing stage companies, it is reasonable to conclude that it does not believe in the near-term turnaround in the overall sector, otherwise the company would wait for said turnaround and acquire the assets at a discount. After all, development stage companies like those mentioned are likely to fall further than mega caps such as Celgene. So, why are we discussing this? Well, Celgene has done it again. This time with a $7.2 billion acquisition of Receptos Inc (NASDAQ:RCPT) – its biggest spend so far this year and one that underlines its market outlook. So, with all this said, what is the deal look like, and how can investors on either side of it expect to fare near-term? Let’s take a look.

So, first up, let’s look at the agreement itself. For those poised with a fine tooth comb, you can see the 8K filing here, however, here is a simple outline of what’s involved. Celgene is to acquire all the outstanding shares of common stock of Receptos at a purchase price of $232 per share. At market close on Tuesday, just before the announcement, Receptos hit $207 a share, meaning Celgene is paying a little over a 12% premium on market rate. However, with around 31.5 million shares outstanding, it is reasonable to conclude that if Celgene was to actually purchase the shares in the open market, we would have seen more than 12% increase in price throughout purchase period. Therefore, it is reasonable to say that Celgene got market, is not slightly below market, rate on its latest acquisition – a far cry from the aforementioned Juno deal. In connection with the acquisition, JPMorgan Chase Bank has committed to providing Celgene with an unsecured bridge loan facility of up to $5 billion, which will cover two thirds of the costs of Receptos.

So what does Receptos bring to the table? Well, this is where things get interesting. The company’s primary focus is autoimmune drug development, and it currently has five candidates in its pipeline. The leader of these candidates – and the one which it is reasonable to conclude Celgene has paid so much for the acquisition of – is RPC1063, an orally administered modulator and trafficking agent currently targeted at the treatment of relapsing multiple sclerosis and two chronic, autoimmune, GI inflammatory disorders; Ulcerative colitis (“UC”) and Crohn’s disease (“CD”). In both instances, the treatment modulates the receptor pathway on white blood cells, and in doing so, achieveds sequestration (a complicated word for separation) of water reactive lymphocytes (responsible for disease proliferation) and the area in the body around which the disease resides. Basically, the treatment stops autoimmune diseases from spreading. Receptos initiated a phase 3 trial called SUNBEAM for RPC1063 in its MS incidence back in December 2014, and an update is expected during the third quarter of this year. For the UC and CD incidences, we saw a very promising results from a phase 2 trial that concluded last year, with the standout figure being 58.2% of patients on the 1 mg dose of RPC1063 achieved clinical response, as compared to 36.9% of patients on placebo. Again, during the third quarter this year, the company plans to initiate phase 3 trials for both of these targets.

So, the big question is, has Celgene overpaid for its new asset? The answer is – at present at least – a resounding no. The company expects to hit peak sales for RPC1063 (assuming approval) of more than $6 billion annually, and with the addition of the extended pipeline, expects net annual product sales in excess of $21 billion within the next five years.

Now back to the initial question: what does the deal look like from investors on both the Celgene and Receptos side of the deal? Well, from a Celgene perspective, it looks like a blockbuster acquisition. The company can make that its costs in a little over 18 months upon approval of RPC1063, and has diversified its current portfolio, which is heavily reliant on just a handful of treatments. From a Receptos perspective, the deal looks like an equally good one. Receptos shares have gained nearly 450% over the last 12 months on buyout rumors, and longer-term holders are now able to sell at this rate of gain, without fear that large scale selling will drive down price per share. All in all, a good deal all round. Well, assuming, that is, that approval follows.

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Anacor Soars; The Two Sides of the Investor Coin

By
ME Staff
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Anacor Pharmaceuticals

On Monday, July 13, 2015, we heard an Anacor Pharmaceuticals Inc. (NASDAQ:ANAC) topline results announcement from two phase 3 studies of one of the company’s lead pipeline candidates. Premarket, the stock traded from its Friday close a rate of four dollars a share to Monday’s open at $117 a share – a 40% gain, and continue to pick up strength throughout the day, eventually closing at $131 – a 56% gain in what effectively amounts to one US session. A couple of questions face investors going forward, let’s try and answer these by way of an investigation into the company and its potentially successful candidate. First of all, let’s outline the questions. The first is for those who held Anacor stock prior to the announcement and who are now more than 55% up on their position. Should they take some profit or hold on for further gains? The second is for those who do not yet have an exposure to the company. Is the candidate likely to receive FDA approval, and – in turn – is their further upside potential medium to long-term? Let’s take a look.

The treatment in question is a topical ointment called Crisaborole, an anti-inflammatory, non-steroidal PDE-4 inhibitor targeting patients with mild to moderate atopic dermatitis. Also called atopic eczema, atopic dermatitis is a common type of eczema that causes inflammation, cracking, itchiness and pain in patients. The treatment works by inhibiting an enzyme called phosphodiesterase 4 (“PDE-4”), and through this inhibition, reducing the production of what’s called tumor necrosis factor alpha (TNF-alpha). TNF-alpha is widely regarded as one of the primary precursors of inflammatory skin diseases such as psoriasis and eczema, and Anacor hypothesizes that its innovation can also lead to a reduction in severity of the aforementioned atopic dermatitis. So, did the trials support this hypothesis?

Over the past 12 months or so, the company has trialed the treatment across two primary phase 3 pivotal studies, each of which studied in the 750 patients each of ages two years or over. Using an Investigator Static Global Assessment (“ISGA”) score, Anacor targeted a primary endpoint of efficacy, defined by the ISGA score. ISGA is an industry standard scoring method which alters depending on what is being tested. In this instance, the score was based on erythema, which is reddening of the skin caused by irritation and causing dilation of blood capillaries. The score split into two potential results that qualified as meeting the endpoint – 0 meaning clear and 1 meaning almost clear. In the first of the trials, we saw 30.8% of patients achieving one of these two scores, the second 31.4%, versus a vehicle rating of 25.4% and 18% respectively. Regarding secondary endpoints, these also used the same scoring system but did not require the candidates to be a minimum of two base points above starting point. In this instance, we saw results of 51.7% 48.5%, and again, these beat the vehicle alternatives of 40.6% for the first study and 29.7% for the second study. Alongside the release, Paul L. Berns, Chairman and Chief Executive Officer of Anacor said:

“We are extremely pleased by the top-line results from our Phase 3 pivotal studies of crisaborole. We believe there is a significant unmet medical need for a novel non-steroidal topical anti-inflammatory treatment option for the patients who are affected by mild-to-moderate atopic dermatitis.”

The company plans to file a new drug application for the treatment during the first half of 2016, and it is this fact that answers the first of our questions – should current holders remain exposed. The answer, is that it could be worth taking some profit of the table, as a number of other exposures will likely do the same on the basis that we will probably not have too much market moving news over the next seven or eight months. This means that a correction is likely short term at least, and offers the opportunity to take profits now and get in at a discounted exposure once the correction completes. Looking longer-term, with a view to answering the second question, there are about 20 million people suffering from atopic dermatitis in the US, and approximately 90% of these suffer from the disease on a mild-to-moderate level, meaning they are potential candidates for this treatment. While price points have not yet been revealed, it is likely that this treatment would fall under the affordable care act in the US, and – as such – with 20 million patients suffering, it could very easily become a $1 billion candidate for Anacor on approval. With this in mind, the answer to the second question – i.e., does the company have more upside potential going forward – has to be yes. Once again, it may be worth waiting for the inevitable correction as short-term speculative holders take profits of table, and then getting in at a discounted price on a medium to long-term exposure.

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The How, What and When of Semaglutide

By
ME Staff
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novo
novo

At the end of last week, we learned that Denmark based Novo Nordisk A/S (ADR) (NYSE:NVO) had achieved promising results in its once weekly diabetes candidate. The treatment, referred to currently as semaglutide, is the latest in a line of diabetes treatments that have come out of the Novo labs, and – according to the company – is considered critical as far as maintaining a strong lead in the diabetes space is concerned. It’s been awhile since we looked at a phase 3 treatment for a company as big as Novo, but this is not through lack of investment opportunity. While it is true that phase 3 approval would mean a lot more as far as short-term upside potential was concerned for a development stage junior biotech, an approval can translate to some upside momentum even in a company of this size. So, with this said, let’s have a look at the treatment, what it does, how it performed in the latest trials, and what potential impact it might have on Novo’s market capitalization going forward – assuming approval.

So, what is semaglutide all about? Well, it is a modern take on the traditional treatment called Glucagon-like peptide-1 agonists, or more succinctly, GLP-1 analogues. There are a number of already approved GLP-1 analogues already available for the treatment of type II diabetes, including the two most famous, Tanzeum, approved in 2014 and marketed by GlaxoSmithKline (NYSE:GSK) and Trulicity, approved in 2014 and marketed by Eli Lilly (NYSE:LLY). However, Novo’s treatment differs from these two in one key area, which we will look at once we’ve addressed its mechanism of action.

As mentioned, semaglutide is a GLP-1 analogue, which means it is an agonist of the glucagon-like peptide 1 receptor (“GLP1R”). GLP1R is a gene inside the human body expressed in pancreatic cells that – when activated – stimulates what’s called the adenylyl cyclase pathway, which is an enzyme pathway responsible for a number of key regulatory roles in pretty much every cell in the human body. One of these roles is the production of insulin. Semaglutide is an agonist, which means that (unlike inhibitors, which stop genetic expression) it promotes expression, and in this instance, boosts insulin production. An increasing so the production in the human body translates to manageable blood sugar levels, hence its efficacy in treating diabetes. Okay, so where does this treatment have an advantage over those already approved? Well, a number of the currently approved treatments require dosages of every other or every three days throughout the week. This frequent dosage can translate to some pretty nasty side-effects, including (using the example of those mentioned above) nausea, diarrhea, kidney issues and – sometimes – pancreatitis. Novo believes that through reduction of dosage and dosing, it can reduce the side-effects associated with its GLP-1 analogues when compared to those currently available. Further, Novo currently has a GLP-1 treatment on the market – Victoza – that is a once-daily treatment. The new alternative offers even larger benefits over this already approved treatment than it does those currently approved with other companies. So what did we see in the trials? In a phase 3a, we saw an improvement of 1.5% and 1.6% for doses of 0.5 mg and 1.0 mg of semaglutide respectively, in patients with baseline HbA1c reading of 8.1%. HbA1c is a type of hemoglobin they can be used to measure blood glucose levels over a period of time, and in turn, can be used to determine efficacy of a particular diabetes treatment. Further, we saw an associated weight loss with the treatment. From the mean baseline and 90 kg, individuals on the smaller dose lost 3.8 kg and those on the larger dose lost 4.6 kg in weight. This compares for weight loss of an average of 1 kg for placebo patients.

And what can we expect going forward? Well, there is a snag, but one that is not impossible to overcome. Basically, this new treatment is a combination of the one we have already mentioned Victoza, and something called degludec. The latter of these two is not yet approved in the US, although it is approved in Europe under the name Tresiba. Before we see semaglutide approved, we will likely have to see degludec approved. An application is with the FDA at the moment, having been submitted in April, but it could be the end of the year before we get the final go-ahead. Having said this, if we do get a yes, there are currently 30 million people in the US suffering from diabetes Type II, and analysts expect Novo to generate more than $1 billion in revenue from the treatment. For a company generating a little over $12 billion annually, this could be a real blockbuster move forward for Novo, and in turn, any investors looking to take a speculative position of the approval of semaglutide. One to watch, definitely.

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