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Guidance, Financing Demolish Short Thesis For BioCryst Pharmaceuticals (NASDAQ:BCRX)

Guidance, Financing Demolish Short Thesis For BioCryst Pharmaceuticals (NASDAQ:BCRX)

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The Company

BioCryst (NASDAQ: BCRX) develops novel, oral, and little molecules that inhibit enzymes playing a crucial part in the organic pathways of unusual disorders. BioCryst has created a environment-class profits workforce to start their flagship products, Orladeyo, for the treatment method of hereditary angioedema (HAE) in the US and EU. The business has also proactively signed a robust stability of promoting partners to support launch Orladeyo in international geographies these types of as Japan and the UAE. BioCryst has hired dozens of field industry experts with about 10 decades of uncommon illness income experience to assistance commercialize Orladeyo, with numerous of these income executives owning been poached from rivals that are also offering HAE therapies. For case in point, BioCryst’s vice-president and US standard manager, Allen Hodge, was responsible for the profitable commercialization of Cinryze and Firazyr, which ended up two revolutionary injectable treatments for HAE. You could not get a additional promising leader for this activity. The depth of working experience at this time becoming recruited to change BioCryst into the subsequent uncommon ailment big is amazing and the enterprise has hired 31 individuals last month, with 59 open positions however remaining advertised on their web page.

The Latest financing

Royalty Pharma (Nasdaq:RPRX) and OMERS Money Markets introduced a non-dilutive credit rating financial investment that resulted in $350 million of clean funding for BioCryst. The resources from these transactions will empower more advancement of BCX9930, BioCryst’s oral Aspect D inhibitor. This will now enable the progress of BCX9930 throughout a number of indications and guidance more financial investment in the world-wide launch of Orladeyo, which is on a trajectory to grow to be the marketplace-foremost prophylactic HAE therapy. For a $150 million upfront dollars payment, Royalty Pharma, the largest consumer of pharmaceutical royalties globally, has acquired royalties on mixed annual net revenue of BCX9930 and a further earlier stage Issue D inhibitor of 3.% on sales up to $1.5 billion, 2.% on sales concerning $1.5 billion and $3. billion, and no royalty on sales over $3. billion. Royalty Pharma also bought royalties of .75% on direct yearly net profits of Orladeyo up to $350 million, 1.75% on product sales amongst $350 million and $550 million, no royalty on gross sales above $550 million, and a tiered, declining percentage on ORLADEYO sublicense income in particular territories. The current $350 million investment decision from Royalty Pharma is their second funds determination to BioCryst and a follow-on expenditure on the royalties they at first purchased in December 2020, which irrefutably demonstrates their significant diploma of conviction in BioCryst’s shiny upcoming.

The Blind Location

To date, Wall Road has projected extremely conservative estimates for sales of Orladeyo. These estimates have been so off, that analyst Jacob Hughes asked how Wall Avenue got their estimates so wrong all through a Wells Fargo conference on September 10, 2021. Jon Stonehouse, CEO of BioCryst, replied, “Wall Street refused to listen to all of the market place investigation BCRX experienced meticulously shared with Wall Avenue for many years.” Handful of analysts had been able to feel the stress of therapy is much extra vital than any other aspects when it arrives to rare illness therapeutics. Analysts myopically lean on clinical demo results, although fully ignoring info on what variety of remedies are in demand from customers in the serious entire world. In reality, the need for oral remedy will constantly supersede the need for injectable remedy.

Orladeyo

On December 3, 2020, the US granted acceptance to Orladeyo for cure of HAE with zero label remarks, which means that they had no worries about side consequences or adverse occasions. Japan, the EU, and the British isles all followed suit with approving Orladeyo soon afterward. With the all over the world acceptance of Orladeyo for the treatment method of HAE, BioCryst is last but not least poised to dollars in on around 20 a long time of R&D. Orladeyo is the very first oral, as soon as-everyday, smaller molecule kallikrein inhibitor positioned to seize a important share of a multibillion-dollar addressable global marketplace. This market is expected to mature to $3.8 billion by 2025. The HAE market place is at the moment dominated by Takeda (NYSE:TAK) and CSL Behring LLC which provide injectable therapies. These therapies involve intravenous (IV) or subcutaneous administration which is hugely invasive and time-consuming. The HAE marketplace is clambering for an oral remedy and Orladeyo is below to fill that void. The current options value roughly $600,000 per calendar year, even though BioCryst is charging $485,000 per year for its everyday oral capsule. In the US, there are at the very least 10,000 individuals with HAE, nevertheless only 7,500 are at this time being treated. There has also been a peer-reviewed study finding that 98% of IV prophylactic clients (the 7,500) would like an oral treatment method and 96% of the non-prophylactic clients (the 2,500) would want an oral therapy. As demonstrated on Web site 13 of the January 2021 Corporate Presentation, 59% of people expressed a higher willingness to use Orladeyo and the selection rose to 71% with physician tips. On May well 12, 2021,BioCryst introduced that the United Kingdom’s Medications and Health care products and solutions Regulatory Agency (MHRA) has granted marketing authorization for oral, as soon as-day by day ORLADEYO™ (berotralstat) for the schedule prevention of recurrent hereditary angioedema attacks in HAE people 12 many years and older. “HAE Uk welcomes the determination from the MHRA to grant advertising authorization for berotralstat in the United kingdom. Hereditary angioedema is an unpredictable and life-threatening affliction that causes major psychological and financial burdens on persons with HAE and their people and professions. These burdens negatively influence their psychological health and fitness and perfectly-getting, on leading of the bodily demands of dwelling with a serious problem. An oral remedy that displays helpful management of HAE assaults will deliver a distinctive procedure decision for clinicians and sufferers and will help in increasing the quality of everyday living of these residing with the affliction,” said Laura Szutowicz, main executive officer of HAE British isles. On September 9th 2021, announced that the Ministry of Well being and Prevention (MOHAP) in the United Arab Emirates (UAE)granted internet marketing authorization for oral, when-daily ORLADEYO® (berotralstat) for the prevention of recurrent assaults in patients with hereditary angioedema 12 a long time and more mature. To assistance commercialization initiatives in the UAE, BioCryst has entered into a supply and distribution agreement with NewBridge Prescription drugs (NewBridge), which also covers the Gulf Cooperation Council and Iraq.

Present Efficacy level of Orladeyo

A new extensive-expression efficacy and safety info from scientific studies assessing oral, after-day by day ORLADEYO® (berotralstat) for the prophylactic procedure of hereditary angioedema, together with outcomes exhibiting sustained reduction of HAE assault costs and improved affected individual pleasure after individuals switched to ORLADEYO monotherapy from injectable prophylactic therapies (lanadelumab and C1 inhibitors). “We keep on to see improvement in key indicators that exhibit the value of oral, as soon as-daily ORLADEYO as an fantastic alternative for patients who want possibilities to injectable prophylactic therapies, which have a significant therapy stress,” reported Dr. William Sheridan, chief healthcare officer of BioCryst. “The information we are presenting at ACAAI even more help ORLADEYO as a transformative treatment for HAE people, such as those who are previously very well-controlled on other therapies.” “The details from APeX-S showed that HAE patients who switched to ORLADEYO from an injectable prophylactic remedy experienced more than 80 per cent assault-free months,” claimed Marc Riedl, M.D., scientific director of the US HAEA Angioedema Center at the College of California San Diego. “These info clearly show that, irrespective of which therapy sufferers switched from, or when they switched, ORLADEYO offered persistently very low attack fees when made use of as a monotherapy. These significant findings add to serious-environment evidence that this oral, after-day by day therapy is a beneficial remedy possibility for quite a few HAE people. “Increased fulfillment and enhancement in good quality of everyday living keep on to be key driving variables for sufferers who determine to swap to an oral prophylactic choice, as demonstrated in our investigation of patients who switched from injectable prophylaxis to ORLADEYO in APeX-2,” explained Jonathan Bernstein, M.D., professor of medicine, office of internal drugs, division of allergy & immunology at the College of Cincinnati and companion of the Bernstein Allergy Team and Bernstein Clinical Analysis Center. “These final results underscore what I see each working day in medical follow, that HAE patients want a more convenient procedure option to control their HAE assaults and lower their all round load of remedy.”

BioCryst ACAAI 2021 Orladeyo Presentation Highlights

  • Highlights security, success, and individual-noted outcomes of ORLADEYO 150 mg in U.S. individuals from APeX-S who accomplished 12 months of treatment (n=71).

  • Pursuing initiation of ORLADEYO, people professional lower HAE assault rates that had been sustained all over the procedure interval (median attack fee of . attacks for every thirty day period via month 12), regular with previously reported info.

  • ORLADEYO was involved with prompt, sustained, statistically considerable, and clinically meaningful improvements in quality of existence (-10.8 change from baseline at month 1 and -13.6 modify 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.

Alternative Pathway

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)

  • Lupus Nephritis

  • IgAN vasculitis

  • C3G (Glomerulonephritis)

  • 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.

The Trials

REDEEM-1

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

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.

Basket Study

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.

Valuation

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

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

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.

Conclusion

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.