BioCryst (NASDAQ: BCRX) develops novel, oral, and tiny molecules that inhibit enzymes enjoying a important function in the biological pathways of unusual disorders. BioCryst has built a earth-course profits workforce to launch their flagship product, Orladeyo, for the treatment method of hereditary angioedema (HAE) in the US and EU. The firm has also proactively signed a strong harmony of advertising and marketing associates to assist launch Orladeyo in foreign geographies these as Japan and the UAE. BioCryst has employed dozens of sector gurus with around 10 decades of scarce disease profits working experience to assist commercialize Orladeyo, with quite a few of these profits executives acquiring been poached from opponents that are also providing HAE therapies. For instance, BioCryst’s vice-president and US common supervisor, Allen Hodge, was responsible for the productive commercialization of Cinryze and Firazyr, which ended up two groundbreaking injectable therapies for HAE. You could not get a a lot more promising chief for this endeavor. The depth of experience currently becoming recruited to flip BioCryst into the up coming scarce disorder large is amazing and the enterprise has employed 31 individuals previous month, with 59 open positions nevertheless being marketed on their website.
The Recent financing
Royalty Pharma (Nasdaq:RPRX) and OMERS Funds Marketplaces declared a non-dilutive credit expense that resulted in $350 million of clean funding for BioCryst. The money from these transactions will help further more progression of BCX9930, BioCryst’s oral Component D inhibitor. This will now let the progress of BCX9930 across numerous indications and assist supplemental investment in the world wide launch of Orladeyo, which is on a trajectory to become the industry-primary prophylactic HAE therapy. For a $150 million upfront cash payment, Royalty Pharma, the largest customer of pharmaceutical royalties globally, has bought royalties on blended annual net gross sales of BCX9930 and an additional earlier phase Issue D inhibitor of 3.% on revenue up to $1.5 billion, 2.% on revenue concerning $1.5 billion and $3. billion, and no royalty on sales about $3. billion. Royalty Pharma also purchased royalties of .75% on immediate yearly web revenue of Orladeyo up to $350 million, 1.75% on profits amongst $350 million and $550 million, no royalty on sales above $550 million, and a tiered, declining percentage on ORLADEYO sublicense profits in specified territories. The the latest $350 million financial investment from Royalty Pharma is their 2nd funds motivation to BioCryst and a stick to-on expenditure on the royalties they at first obtained in December 2020, which irrefutably demonstrates their substantial diploma of conviction in BioCryst’s bright future.
The Blind Spot
To day, Wall Road has projected pretty conservative estimates for income of Orladeyo. These estimates were being so off, that analyst Jacob Hughes requested how Wall Road acquired their estimates so completely wrong throughout a Wells Fargo convention on September 10, 2021. Jon Stonehouse, CEO of BioCryst, replied, “Wall Street refused to listen to all of the market place investigate BCRX had meticulously shared with Wall Avenue for decades.” Few analysts were being ready to think the load of procedure is significantly much more significant than any other factors when it arrives to unusual ailment therapeutics. Analysts myopically lean on scientific trial benefits, even though entirely disregarding details on what sort of remedies are in demand in the real environment. In actuality, the demand for oral therapy will constantly supersede the need for injectable remedy.
On December 3, 2020, the US granted acceptance to Orladeyo for treatment of HAE with zero label comments, which means that they experienced no worries about facet consequences or adverse events. Japan, the EU, and the Uk all adopted go well with with approving Orladeyo soon afterward. With the throughout the world acceptance of Orladeyo for the therapy of HAE, BioCryst is last but not least poised to hard cash in on over 20 decades of R&D. Orladeyo is the 1st oral, the moment-day by day, little molecule kallikrein inhibitor positioned to capture a considerable share of a multibillion-dollar addressable international market. This market place is predicted to expand to $3.8 billion by 2025. The HAE marketplace is at the moment dominated by Takeda (NYSE:TAK) and CSL Behring LLC which present injectable therapies. These therapies involve intravenous (IV) or subcutaneous administration which is remarkably invasive and time-consuming. The HAE sector is clambering for an oral option and Orladeyo is here to fill that void. The existing solutions expense close to $600,000 per 12 months, when BioCryst is charging $485,000 for every yr for its daily oral tablet. In the US, there are at the very least 10,000 folks with HAE, however only 7,500 are at present remaining handled. There has also been a peer-reviewed study discovering that 98% of IV prophylactic people (the 7,500) would like an oral remedy and 96% of the non-prophylactic clients (the 2,500) would want an oral treatment method. As shown on Web site 13 of the January 2021 Company Presentation, 59% of individuals expressed a significant willingness to use Orladeyo and the quantity rose to 71% with medical professional tips. On Could 12, 2021,BioCryst declared that the United Kingdom’s Medicines and Healthcare items Regulatory Agency (MHRA) has granted advertising and marketing authorization for oral, after-day-to-day ORLADEYO™ (berotralstat) for the regime avoidance of recurrent hereditary angioedema assaults in HAE sufferers 12 several years and more mature. “HAE British isles welcomes the selection from the MHRA to grant promoting authorization for berotralstat in the United kingdom. Hereditary angioedema is an unpredictable and existence-threatening condition that causes significant emotional and financial burdens on people today with HAE and their families and occupations. These burdens negatively affect their mental wellbeing and well-staying, on major of the physical calls for of residing with a continual affliction. An oral treatment that displays effective regulate of HAE attacks will provide a various remedy alternative for clinicians and patients and will guide in improving upon the good quality of lifetime of people living with the situation,” reported Laura Szutowicz, chief govt officer of HAE United kingdom. On September 9th 2021, announced that the Ministry of Overall health and Prevention (MOHAP) in the United Arab Emirates (UAE)granted marketing authorization for oral, the moment-day-to-day ORLADEYO® (berotralstat) for the avoidance of recurrent assaults in clients with hereditary angioedema 12 decades and older. To guidance commercialization initiatives in the UAE, BioCryst has entered into a source and distribution arrangement with NewBridge Pharmaceuticals (NewBridge), which also addresses the Gulf Cooperation Council and Iraq.
Latest Efficacy degree of Orladeyo
A new very long-phrase efficacy and protection details from studies evaluating oral, as soon as-each day ORLADEYO® (berotralstat) for the prophylactic remedy of hereditary angioedema, like success demonstrating sustained reduction of HAE attack costs and enhanced affected person pleasure immediately after patients switched to ORLADEYO monotherapy from injectable prophylactic therapies (lanadelumab and C1 inhibitors). “We continue on to see improvement in important indicators that demonstrate the worth of oral, when-everyday ORLADEYO as an great selection for clients who want choices to injectable prophylactic therapies, which carry a high treatment method burden,” mentioned Dr. William Sheridan, main health-related officer of BioCryst. “The information we are presenting at ACAAI more assist ORLADEYO as a transformative therapy for HAE clients, which include these who are now effectively-controlled on other therapies.” “The details from APeX-S showed that HAE individuals who switched to ORLADEYO from an injectable prophylactic treatment experienced more than 80 per cent assault-free months,” reported Marc Riedl, M.D., medical director of the US HAEA Angioedema Centre at the University of California San Diego. “These details show that, regardless of which therapy individuals switched from, or when they switched, ORLADEYO furnished consistently lower attack costs when employed as a monotherapy. These vital conclusions increase to serious-planet evidence that this oral, the moment-every day remedy is a advantageous therapy solution for quite a few HAE patients. “Amplified fulfillment and improvement in top quality of everyday living continue on to be key driving components for clients who determine to change to an oral prophylactic possibility, as demonstrated in our analysis of individuals who switched from injectable prophylaxis to ORLADEYO in APeX-2,” explained Jonathan Bernstein, M.D., professor of drugs, division of interior medication, division of allergy & immunology at the University of Cincinnati and spouse of the Bernstein Allergy Group and Bernstein Clinical Investigation Center. “These outcomes underscore what I see every working day in scientific practice, that HAE patients want a additional effortless treatment method solution to handle their HAE assaults and decrease their overall burden of remedy.”
BioCryst ACAAI 2021 Orladeyo Presentation Highlights
Highlights protection, effectiveness, and client-claimed results of ORLADEYO 150 mg in U.S. clients from APeX-S who done 12 months of treatment method (n=71).
Next initiation of ORLADEYO, clients experienced reduced HAE assault prices that were sustained all through the therapy interval (median assault charge of . assaults per month by means of thirty day period 12), regular with previously reported knowledge.
ORLADEYO was linked with prompt, sustained, statistically significant, and clinically significant advancements in high-quality of lifetime (-10.8 improve from baseline at month 1 and -13.6 transform from baseline at months 6 and 12 p<0.001) as measured by the AE-QoL (angioedema quality of life questionnaire) total score. These improvements exceeded the minimal clinically important difference (-6 change).
ORLADEYO was generally well tolerated, with no drug-related serious adverse events reported. The Holy Grail – Pivotal Oral Factor D trials
The Holy Grail – Pivotal Oral Factor D trials
The FDA has granted both Fast Track status and Orphan Drug Designation to BCX9930 for PNH. BioCryst met with regulators in the fourth quarter of 2020 to discuss the advanced development program for BCX9930. The FDA has agreed that the key endpoints of this trial will be raising hemoglobin levels and eliminating the need for transfusions. These data endpoints will prove oral Factor D inhibition as the new standard of care for treating PNH. In BioCryst’s previously published Phase 1 study, it was clear that BCX9930 works much better than all of Alexion’s industry-standard treatments for these endpoints. Unfortunately, Alexion’s PNH treatments struggle to sufficiently raise hemoglobin levels high enough to avoid transfusions. These transfusions are costly and time-consuming for patients. Alexion was also recently acquired for $39 billion by AstraZeneca, primarily for the sales from Alexion’s PNH products.
PNH Efficacy Metrics
The key to the efficacy of this kind of treatment is improving hemoglobin levels. BCX9930 showed 3.8g/dL improvement (page 31). A competitor Novartis (NYSE:NVS) showed 2.87g/dL improvement and Alexion showed 2.4-2.6g/dL.
“In the study, BCX9930 was highly specific for the alternative pathway and, after oral dosing of BCX9930 in primates, alternative pathway activity was completely suppressed.” “These data demonstrate that BCX9930 is a highly potent and specific orally bioavailable Factor D inhibitor with potential for the treatment of patients with PNH and other alternative pathway-mediated diseases,” said Dr. William Sheridan.
What makes BCX9930 a game-changer is the wide spectrum of Alternative Pathway dysregulation diseases it can treat. With the potential to treat up to 8 diseases currently, one quickly understands why Management calls BCX9930 a pipeline in a molecule. Here are the currently announced diseases BCX9930 will seek to treat:
PNH (Paroxysmal nocturnal hemoglobinuria)
aHUS (atypical hemolytic uremic syndrome)
ANCA vasculitis (antineutrophil cytoplasmic antibody-associated vasculitis)
PMN (Primary membranous nephropathy)
IgAN (IgA nephropathy)
The potential market size BCX9930 will be aiming for by 2025 scores up to over $10B annually. That number is obtained by summing up the following:
PNH Treatment Market Size Worth $5.8 Billion by 2025
The global systemic lupus erythematosus market size is expected to reach USD 3.08 billion by 2025
aHUS, having in mind the disease prevalence (2 and 5.5)/MM, and the disease being treated with Soliris – 500,000$/ year. The worldwide market size Vasculitis treatment market size is forecast to reach $743.2M by 2025
IgAN, having in mind the 1/3,707 incidence rate, creates a big opportunity.
C3G can be treated with Soliris and it costs $500,000 a year.
On Jan. 07, 2022, BioCryst announced the enrollment of the first patient for the REDEEM-1 pivotal trial with its oral Factor D inhibitor, BCX9930, in patients with paroxysmal nocturnal hemoglobinuria (PNH). REDEEM-1 is a randomized, open-label, active comparator-controlled comparison of the efficacy and safety of BCX9930 (500 mg bid) monotherapy in approximately 81 PNH patients with an inadequate response to a C5 inhibitor. In part 1 of this trial, patients who have not had an adequate response to a C5 inhibitor will be randomized 2:1 to discontinue their C5 inhibitor and receive BCX9930 as monotherapy or to continue receiving their C5 inhibitor for 24 weeks. All patients will receive BCX9930 in part 2 (weeks 25-52) to assess the long-term safety, tolerability, and effectiveness of BCX9930. Patients who are randomized to C5 inhibitor therapy in part 1 will discontinue that therapy at the week 24 visit and start BCX9930 for part 2. The primary endpoint of REDEEM-1 is a change from baseline in hemoglobin, as assessed at weeks 12 to 24.
“On the heels of recently beginning enrollment in our REDEEM-2 pivotal trial, today’s announcement marks another important milestone as we advance BCX9930 closer to registration for patients living with PNH,” said Dr. William Sheridan, chief medical officer of BioCryst. “Given the unmet need patients have related to the current standard of care, we aim to demonstrate in the REDEEM-1 pivotal trial the potential of BCX9930 as an oral monotherapy that could represent a significant improvement for patients compared to their experiences with C5 inhibitor therapies.”
In a dose-ranging trial of BCX9930 in C5 inadequate response patients, the company previously reported that BCX9930 (at doses of 400 mg or 500 mg bid) increased hemoglobin from baseline by a mean of 2.7 g/dL through weeks 12 to 24 with 80 percent of patients being transfusion-free over the same period. BCX9930 was safe and generally well-tolerated in the trial.
REDEEM-2 is a randomized, placebo-controlled trial evaluating the efficacy and safety of BCX9930 (500 mg bid) as monotherapy versus placebo in approximately 57 PNH patients not currently receiving complement inhibitor therapy. In part 1 of this trial, patients will be randomized 2:1 to receive BCX9930 or placebo under double-blind conditions for 12 weeks. All patients will receive BCX9930 in part 2 (weeks 13-52) to assess the long-term safety, tolerability, and effectiveness of BCX9930, with patients randomized to placebo in part 1 switching to BCX9930 at the week 12 visit. The primary endpoint of REDEEM-2 is a change from baseline in hemoglobin, as assessed at week 12. “There are important unmet needs among patients living with PNH based on the current standard of care, specifically related to efficacy and burden of therapy. As an oral monotherapy with proof-of-concept data showing control of both intravascular and extravascular hemolysis, BCX9930 has the potential to help patients live their lives with more freedom from their disease,” said Dr. William Sheridan, chief medical officer of BioCryst. “Beginning patient enrollment in our REDEEM-2 pivotal trial marks a critical step forward as BCX9930 advances closer to registration for patients living with PNH,” Sheridan added.
REDEEM-2 is powered at 90 percent to detect a difference in mean change from baseline of hemoglobin of ≥ 2.15 g/dL at 12 weeks. In a dose-ranging trial of BCX9930 in treatment-naïve patients, the company previously reported that BCX9930 (at doses of 400 mg or 500 mg bid) increased hemoglobin from baseline by a mean of 3.7 g/dL at week 12 and eliminated transfusions. BCX9930 was safe and generally well-tolerated in the trial.
BioCryst will also soon initiate a proof of concept trial of oral BCX9930 (500 mg bid) in renal complement-mediated diseases. The trial will be a Phase 2 basket study including cohorts of patients with C3 glomerulopathy, IgA nephropathy, and primary membranous nephropathy.
Preliminary 4th Quarter highlights
BioCryst announced preliminary, unaudited ORLADEYO® (berotralstat) revenue for the fourth quarter and full-year 2021, while providing new guidance for full-year 2022 ORLADEYO net revenue and expected peak ORLADEYO sales.
“Following 12 months of a successful launch through a global pandemic, we have a clear picture of the continued commercial trajectory for ORLADEYO based on a very attractive product profile, leading to strong patient demand to switch from injectable therapies to our oral, once-daily medicine, with 70 percent patient retention through the first year. Building on our substantial 2021 patient base, we are confident that ORLADEYO will achieve no less than $250 million of net revenue in 2022 and that ORLADEYO will become the market leader as the most prescribed prophylactic therapy with peak sales of $1 billion,” said Jon Stonehouse, president, and chief executive officer of BioCryst.
Fourth Quarter 2021 (Q4 2021) ORLADEYO Launch Dynamics
Preliminary, unaudited ORLADEYO net revenue in Q4 2021 was $45.6 million. Preliminary, unaudited ORLADEYO net revenue for full-year 2021 (FY 2021) was $122 million.
New patient demand for ORLADEYO remains strong and consistent, with a similar number of new patients added in Q4 2021 as in each of the previous three quarters of the year. Patients switching from other prophylactic therapies and acute-only therapy continue to drive the launch. More than half of patients new to ORLADEYO since launch had a previous prophylactic medicine prior to ORLADEYO and most of the remainder were from acute-only treatment.
Most patients are well-controlled on ORLADEYO and remain on therapy. Approximately 70 percent of patients starting ORLADEYO, including those switching from injectable prophylaxis, remain on ORLADEYO in the first year.
ORLADEYO is now covered by all major payors and national and regional pharmacy benefit managers, which will lead to more patients being reimbursed quickly.
The ORLADEYO prescriber base continues to grow significantly. The number of new physicians prescribing ORLADEYO in Q4 2021 was similar to the number added in Q3 2021. In market research, 60 U.S. physicians, who treat an average of seven HAE patients each, reported that they expect to double their use of ORLADEYO, and that ORLADEYO will become their most prescribed prophylactic treatment in the next 12 months.
“We expect ORLADEYO revenues in 2022 to more than double in our second year of launch as we benefit from a full year of reimbursement and continued strong demand from patients and physicians. ORLADEYO is transforming the lives of HAE patients, which is why ORLADEYO is on a trajectory to become the market leader in HAE prophylaxis,” said Charlie Gayer, the chief commercial officer of BioCryst.
Pipeline Update: BCX9930 Pivotal Trials in PNH Now Enrolling
BioCryst is currently enrolling patients in two global pivotal trials, REDEEM-1, and REDEEM-2, with the company’s oral Factor D inhibitor, BCX9930 (500 mg bid), in patients with paroxysmal nocturnal hemoglobinuria (PNH). The company also has begun screening patients in a proof of concept (POC) basket trial of BCX9930 (500 mg bid) in patients with C3 glomerulopathy (C3G), IgA nephropathy (IgAN), and primary membranous nephropathy (PMN).
BioCryst plans to further advance and expand its Factor D program over the next two years by achieving the following:
Complete and report data from REDEEM-1 and REDEEM-2
Prepare to submit regulatory approval filings in PNH
Complete the renal PoC basket trial and advance to pivotal trials in C3G, IgAN and PMN
Commence PoC trials in other complement-mediated diseases
“Following the discovery, development, and commercialization of ORLADEYO, the BioCryst team plans to repeat this success as we leverage our platform to bring new oral medicines to patients suffering from other rare diseases. BCX9930 is especially exciting because the clinical data we have reported so far provides confidence that we can help patients in PNH, and across many complement-mediated diseases, with this pipeline in a molecule,” said Dr. Helen Thackray, chief research and development officer of BioCryst.
BCRX has approximately 185 million shares outstanding and has a current price of $15.25 a share. This means BioCryst has a current market value of $2.8 billion. It is extremely hard to value an evolving drug pipeline, but I will try to give a conservative estimate.
Galidesivir is an antiviral that is currently being funded and studied by BARDA. The purpose of this effort is for BARDA to find a broad-spectrum antiviral to stockpile against possible bio attacks. The government has awarded a total of $147 million to study this drug. Galidesivir could easily be worth $2-6 billion with the right approval.
Orladeyo has the US, Japanese, EU, and UK approval. Being the only oral treatment for HAE, Orladeyo could easily gain 30-70 percent market share of a current $1.5 billion market. This market is anticipated to grow to $3.8 billion by 2025. Orladeyo could have sales of $1 to $1.5 billion by 2024 and potentially $2-4 billion by 2025. Based on these sales, BCRX easily garners a multiple of 8-12 times sales. This would equate to $7.5 billion on the low side to $30 billion on the high side.
BCX9930 Oral Factor D the Ultimate burden of proof play
“While Orladeyo is currently moving the needle and taking the spotlight, it will soon be upstaged by one of the most dominant drugs to hit the rare blood disorder market. BCX9930 is the real pride and joy of BioCryst and for very good reason. The touted “pipeline in a molecule” is showing unprecedented efficacy in early stages and has more than proven itself a behemoth in the rare disease space with its recent PNH results giving patients a taste of transfusion-free freedom.
While PNH is the current main target indication for BCX9930, the company is also putting the drug into a basket of renal diseases to show just how flexible this drug can be. A twice-a-day oral pill has the ability to change patients’ lives in a way never done before with these rare blood disorders giving them freedom from the burden of treatment.
For example, in PNH alone, patients often have to go into the clinic two to three times a week to receive infusions from a medical professional. These are NOT able to be administered at home and often leave patients waiting in long lines at the hospital or clinic for treatment. A simple 2-hour infusion often takes 4 to 5 hours per treatment, adding into 10 to 15 hours of wasted time every single week for patients to get any sort of relief. That all changes with BCX9930 if approved. The drug has proven effective mono-therapy and gives patients their lives back by only having to take a pill twice a day vs hours and hours of treatment every single week.” – Source
This drug could easily be worth 7 to 10 billion according to management. With 1-5 billion in potential sales for more than 10 indications, the upside is unlimited. Oral vs. shots, are not even close according to all the market research.
While it is possible for any biotech company to suffer failure of a drug trial or other unforeseen disappointments leading to share depreciation, BioCryst has proven they know how to nab FDA approvals and bring drugs to the market. I have been covering BCRX since October 27, 2020, when it was trading at $3.73 a share. It was cheap then but nowhere near as cheap as it is now. With the eventual approval of Oral Factor D for PNH, this stock could be worth triple digits. Alexion was bought for $39 billion with far inferior results than BioCryst produced in the 9930 phase 1 PNH trial. These trials have continued and there is now 19-month data showing how effective BCX9930 works. There are at least 10 other rare drug indications BioCryst could directly enter phase 2-3 trials. Safety trials should no longer be needed. The opportunity to possibly invest in an early-stage Regeneron (REGN) should be priceless. The opportunity to buy this stock at reasonable valuations is ending. Pivotal trials are beginning and sales of Orladeyo are ramping up to 250 million-plus per year. Easing the burden of treatment will win every time. Those short twenty-five million shares will soon figure out there is no way out of their predicament until they can find 25 million shares for sale.