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Earnings Call: Coal Refurbishment->Nuclear!
[...]Project Phoenix. And essentially this is to escalate the transition of Europe coal fire plants to SMRs. And the key for this is retaining local jobs. Now, this is not dissimilar from what we’re doing in Romania, in Poland, as well as what we’re going to be doing in the United States. Coal refurbishment is going to be huge opportunity globally for the advanced nuclear community.
Earnings Call: coal to nuclear concept being further embraced as a key strategy to build a new path for our energy communities.
Earnings Call: Ukraine, Ghana...
The discussion included announcement by the U.S. government commands a pilot project in Ukraine that will demonstrate the production of clean hydrogen ammonia using NuScales’ SMR technology carried out by a public private consortium from the U.S., Ukraine, Japan, and the Republic of Korea.
As part of this agreement, the government of Japan has funded a feasibility study and supply chain survey for the potential deployment of a NuScale VOYGR SMR power plant in Ghana. This collaboration that’s the first of a kind on the African continent, a market we believe could be well served by our technology.
SMRs are starting to show up on YouTube/social media.
Here is a recent one:
Ukraine, SMR, COP 27, Kerry
https://www.state.gov/special-presidential-envoy-for-climate-kerry-and-ukraine-minister-of-energy-galushchenko-announce-cooperation-on-a-clean-fuels-from-small-modular-reactors-pilot-cop27-climate-conference/
Special Presidential Envoy for Climate John Kerry and Ukraine Minister of Energy German Galushchenko announced a Ukraine Clean Fuels from SMRs Pilot project that will demonstrate production of clean hydrogen and ammonia using secure and safe small modular nuclear reactor (SMR) and cutting-edge electrolysis technologies in Ukraine.
The project aims to carry out a first-of-a-kind pilot of commercial-scale production of clean fuels from SMRs using solid oxide electrolysis. Building on existing capacity-building cooperation launched under the U.S. Foundational Infrastructure for Responsible Use of SMR Technology (FIRST) program, the project seeks to support Ukraine’s energy security goals, enable decarbonization of hard-to-abate energy sectors through clean hydrogen generation, and improve long-term food security through clean ammonia-produced fertilizers. Further, it aims to demonstrate Ukraine’s innovative clean energy leadership through the use of advanced technologies.
Participating partners for the pilot include a multinational consortium from Argonne National Laboratory, Ukraine’s Energoatom, National Security and Defense Council, and State Scientific and Technical Center for Nuclear and Radiation Safety, and private companies Clark Seed, Doosan Enerbility, FuelCell Energy, IHI Corporation, JGC Corporation, NuScale Power, Samsung C&T, and Starfire Energy.
In a second announcement, Special Envoy Kerry launched a new initiative, Project Phoenix, to accelerate the transition in Europe of coal-fired plants to SMRs while retaining local jobs through workforce retraining. Project Phoenix will provide direct U.S. support for coal-to-SMR feasibility studies and related activities in support of energy security goals for countries in Central and Eastern Europe.
The United States is committed to supporting the use of innovative clean energy technologies to power global decarbonization efforts and providing options to achieve net zero transition in hard-to-abate energy sectors.?
2022 Q3 PDF
https://s29.q4cdn.com/251742275/files/doc_financials/2022/q3/NuScale-Earnings-Deck-Q3-FINAL-v2.pdf
Best of luck with your investments!
Site, Cost
In terms of the large reactor, quickly, we're about one-fifteenth of size.
We'll be about slightly lower on our per kilowatt installed in the capital cost, half the construction time, and able to site these things in a number of places because we have an emergency planning zone that ends at that site boundary, unlike the 10-mile area for a large nuclear plant
We have over 634 patents. When we started the company in 2007, we had three patents. A lot of technology development over the time.
Ample cash for several years of commercialization and deployment.
From the June 23, 2022 JP Morgan Transcripts
https://s29.q4cdn.com/251742275/files/doc_downloads/2022/06/SMR-at-the-J.P.-Morgan-Energy-Power-Renewables-Conference-Transcript.pdf
Matched off by Fluor, who's our largest shareholder, with about 600 million. Then, eight other folks that came in for the balance of that over time, as shown there at the bottom. Again, with the merger we did in May, we raised about $340 million net through that transaction, which was better than we had expected or had hoped for, given a recent SPAC transactions.
Added that to about $40 million in the balance sheet. We have ample cash to carry us through to the next several years of commercialization and deployment.
Q2 2022 CC; Goals, Pipeline
From the Aug. 10th call, John Hopkins:
As a reminder, our five year near-term objectives are
* one, we intend to secure our next committed customer by year-end.
* Two, we intend to issue long lead material specifications for the nuclear reactor pressure vessel.
* Three, we intend to complete the reactor building design.
* Four, we intend to submit a standard design approval application to the U.S. Nuclear Regulatory Commission for the VOYGR-6 module power plant that UAMPS plans deploy.
* Five, we intend to complete our standard plan design, which will also refer to as SPD throughout my remarks.
Now let's look at the progress you made in Q2 towards each of these goals. First, we continue to build a potential customer pipeline. The progress is solid at our anchor customer, UAMPS, in the U.S. and we continue to strengthen our six relationships around the world. Moreover, we have 18 signed and active MOUs in 11 countries and nine strategic relationships.
Some of which I'll discuss in a moment, customer opportunities in a pipeline are now at over 100 and we are happy the level, the discussions we are having across the board.
I am impressed with your demeanor and your patience.
Best of luck with your investments!
Q3 2022: Headwinds - Ukraine, China Covid Policies, Inflation
Third quarter revenue of $60.5 million; nine months 2022 revenue reaches $176.9 million; Cryoport Systems' revenue up 25% year-over-year
$530 million in cash and short-term investments
Supporting a record 643 global clinical trials; 61 net new trials added (year-over-year)
Entered strategic relationship with Takeda's BioLife Plasma Services for apheresis collection and leukopak production
Record number of new products and offerings slated to be released by Cryoport in 2023
Like many companies that operate globally, we were subject to macroeconomic headwinds during the third quarter and expect some of these pressures will extend into the fourth quarter. Specifically, during the third quarter, we experienced a convergence of macroeconomic pressures that impacted revenue including: a negative foreign exchange impact of $2.6 million due to the increased strength of the U.S. dollar against certain foreign currencies; recurring COVID lockdowns in China; supply chain related issues; the Russia/Ukraine war and its ripple effect throughout Europe; and industry capacity limitations, which interfered with cell and gene therapy commercial revenue acceleration.
Bought a few more shares. $1.21 is a great price. My timeline is at least another year for the potential to start getting realized. I will probably put more $$ in on a monthly basis. The train is on the tracks.
I expect a first bump in August; Then the EPS will do the talking, quarter after quarter.
Best of luck with your investments!
OTLK hits its planned dates. Again!
I really like the timeline guidance they provide and how they follow up on them. It's been the case for most (all?) of their planned dates. For this one:
Russ mentioned an end of October response from the FDA in his interview.
And here we are, end of October. They don't schmooze, they execute. It raises the level of trust in the Company.
Best of luck with your investments!
expected 12 years of regulatory exclusivity in the United States
Thanks pfelgueiras for highlighting this part!!!
Best of luck with your investments!
(PDUFA) goal date of August 29, 2023
https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-announces-acceptance-biologics-license
ISELIN, N.J., Oct. 28, 2022 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a Biologics License Application (BLA) for ONS-5010 / LYTENAVA™ (bevacizumab-vikg), an investigational ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD). The FDA set a Prescription Drug User Fee Act (PDUFA) goal date of August 29, 2023. ONS-5010, if approved, is expected to receive 12 years of regulatory exclusivity in the United States.
“This BLA acceptance and PDUFA date are significant milestones in our mission to offer clinicians and their patients the first and only on-label, ophthalmic bevacizumab to treat wet AMD,” said Russell Trenary, President and CEO of Outlook Therapeutics. “If approved, ONS-5010 (bevacizumab-vikg) will meet the robust FDA requirements for use as an ophthalmic injectable. We estimate that approximately 50% of the millions of anti-VEGF injections in ophthalmology are off-label compounded bevacizumab that is administered with no FDA-approved labeling. That product configuration does not meet the same standards we must achieve to earn FDA approval in ophthalmology. We hope to enhance the standard of care in the anti-VEGF space, and we are proud of the entire team and our clinical partners and advisors for bringing ONS-5010 to this point in its journey towards FDA approval.”
“We are pleased the FDA has begun its review of our application. ONS-5010 is designed and manufactured to be fully compliant with the FDA’s criteria for ophthalmic intravitreal biologics and we are excited about the prospect of filling the public health need for an FDA-approved ophthalmic formulation of bevacizumab,” added Terry Dagnon, Chief Operations Officer of Outlook Therapeutics.
As part of the Company’s multi-year commercial planning process, and in anticipation of potential FDA approval in August 2023, Outlook Therapeutics and AmerisourceBergen recently announced a strategic commercialization agreement to expand the Company’s reach for connecting to retina specialists and their patients. AmerisourceBergen will provide third-party logistics (3PL) services and distribution, as well as pharmacovigilance services in the United States. Through this agreement, Outlook Therapeutics expects to increase market access and efficient distribution of ONS-5010, while not duplicating services provided by AmerisourceBergen, thereby decreasing Outlook’s otherwise needed expense for those same services.
Outlook Therapeutics also established best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance manufacturing, and with drug product manufacturer Ajinomoto Bio-Pharma Services for finished drug product.
In addition to the U.S. filing, Outlook Therapeutics is also developing registration documents on a parallel path for approvals in Europe and expects to submit them in the fourth quarter of 2022. Outlook Therapeutics is assessing both direct commercialization and partnering in Europe and Asia on a country-by-country basis.
SA Article
CM in Q4 of 2022. With proof of concept established with omecamtiv mecarbil for heart failure, plus several catalysts expected within a year, these are the reasons why I believe that Cytokinetics is a great speculative biotech play to look into.
Omecamtiv Mecarbil Holds Great Potential With A Few Catalysts
The main drug in the pipeline for Cytokinetics would be omecamtiv mecarbil. That's because not only has it established proof of concept by meeting the primary composite endpoint for the phase 3 GALACTIC-HF study, but it now has two catalysts on the way which traders/investors can focus on. Before going over these catalysts though, it's important to highlight why the biotech was able to move on to file a New Drug Application (NDA) to the FDA. The reason again is because of the impressive results it was able to obtain from the late-stage GALACTIC-HF study. There was a total of 8,256 patients who were recruited that were at risk of hospitalization or death, despite still receiving ongoing standard of care (SOC) therapy. It was noted that omecamtiv mecarbil met on the primary composite endpoint compared to placebo. That is, treatment with Omecamtiv mecarbil reduced the risk of cardiovascular death or heart failure events compared to placebo (patients who received standard of care). With this primary composite endpoint being met, it now provides Cytokinetics the avenue to move towards possible FDA approval. It has already met with the FDA and because additional data was sent to the agency, it needed additional time to review it. Thus, one major catalyst which investors can look forward to would be the PDUFA date established for omecamtiv mecarbil for the treatment of heart failure patients, which is set for February 28, 2023. That's not the only catalyst which investors have to look forward to either. Before this FDA final decision for omecamtiv, the FDA advisory panel committee is going to review the drug first on December 13, 2022. If the advisory committee review goes well, plus the FDA chooses to ultimately approve it for marketing of this heart failure indication, then the expected launch would happen in Q1 of 2023.
SA Article
CM in Q4 of 2022. With proof of concept established with omecamtiv mecarbil for heart failure, plus several catalysts expected within a year, these are the reasons why I believe that Cytokinetics is a great speculative biotech play to look into.
Omecamtiv Mecarbil Holds Great Potential With A Few Catalysts
The main drug in the pipeline for Cytokinetics would be omecamtiv mecarbil. That's because not only has it established proof of concept by meeting the primary composite endpoint for the phase 3 GALACTIC-HF study, but it now has two catalysts on the way which traders/investors can focus on. Before going over these catalysts though, it's important to highlight why the biotech was able to move on to file a New Drug Application (NDA) to the FDA. The reason again is because of the impressive results it was able to obtain from the late-stage GALACTIC-HF study. There was a total of 8,256 patients who were recruited that were at risk of hospitalization or death, despite still receiving ongoing standard of care (SOC) therapy. It was noted that omecamtiv mecarbil met on the primary composite endpoint compared to placebo. That is, treatment with Omecamtiv mecarbil reduced the risk of cardiovascular death or heart failure events compared to placebo (patients who received standard of care). With this primary composite endpoint being met, it now provides Cytokinetics the avenue to move towards possible FDA approval. It has already met with the FDA and because additional data was sent to the agency, it needed additional time to review it. Thus, one major catalyst which investors can look forward to would be the PDUFA date established for omecamtiv mecarbil for the treatment of heart failure patients, which is set for February 28, 2023. That's not the only catalyst which investors have to look forward to either. Before this FDA final decision for omecamtiv, the FDA advisory panel committee is going to review the drug first on December 13, 2022. If the advisory committee review goes well, plus the FDA chooses to ultimately approve it for marketing of this heart failure indication, then the expected launch would happen in Q1 of 2023.
December 13, 2022 as AdCom Date for Omecamtiv Mecarbil,
(from StreetInsider)
PDUFA of February 28, 2023
Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the U.S. Food and Drug Administration (FDA) has informed the company that the previously announced meeting of the Cardiovascular and Renal Drugs Advisory Committee to review the New Drug Application for omecamtiv mecarbil is currently scheduled for December 13, 2022. The FDA has assigned the NDA a Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2023. Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator for the treatment of heart failure with reduced ejection fraction (HFrEF).
SA article / Ph III ALS - DMC recommended Continuation
Same news packaged in a different way on SA:
Cytokinetics (NASDAQ:CYTK) said a data monitoring committee (DMC) recommended the continuation of a phase 3 trial of reldesemtiv to treat amyotrophic lateral sclerosis (ALS), after reviewing unblinded data.
The DMC had assemble to conduct the first planned interim analysis of the ongoing phase 3 study, dubbed COURAGE-ALS, which assessed for the potential of futility.
The first interim analysis was done 12 weeks after about one-third or more of the intended number of patients were randomized to participate in the study.
The study is expected to enroll ~555 patients with ALS who will receive either 300 mg of reldesemtiv or matching placebo dosed orally twice daily for 24 weeks, followed by a 24-week period in which all patients will receive 300 mg of reldesemtiv twice daily.
The main efficacy goal is change from baseline to 24 weeks in the ALS Functional Rating Scale – Revised (ALSFRS-R).
ALS is a progressive nervous system disorder affecting nerve cells in the brain and spinal cord, leading to loss of muscle control.
Continuation of COURAGE-ALS Following First Interim Analysis
October 10 2022 - 07:30AM
GlobeNewswire Inc.
Cytokinetics, Incorporated (Nasdaq: CYTK) today announced that the Data Monitoring Committee (DMC) for COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS), recently convened to conduct the first planned interim analysis of this ongoing Phase 3 clinical trial which assessed for the potential of futility. The DMC reviewed unblinded data from COURAGE-ALS and recommended that conduct of the clinical trial of reldesemtiv continue. Reldesemtiv is a fast skeletal muscle troponin activator (FSTA) in clinical development for the potential treatment of amyotrophic lateral sclerosis (ALS).
The first interim analysis was triggered 12 weeks after approximately one-third or more of the intended number of patients were randomized to participate in COURAGE-ALS.
A second interim analysis, which is anticipated to occur in the first half of next year, will also assess for potential futility and will also allow for a fixed increase in total enrollment, if deemed necessary, to augment the statistical power of the trial.
I expect the PDUFA date as the next news pfelgueiras
After the re-submission
( https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-re-submits-biologics-license-application)
the ball is in the camp of the FDA.
Russ mentioned an end of October response from the FDA in his interview (thanks for the link pfelgueiras!!). That would make sense. OTLK does not control how the FDA proceeds of course, so it's different from other timelines OTLK provided and met.
I expect the FDA to provide a PDUFA date. Then we have a target for approval/launch. a BO could happen anytime as well. There are incentives
( https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167601827 and
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=167601089)
but even if they go it alone, this should be a great ride.
The MC is only $286.95M. If all does fall into place, the MC would end up in multiples (pick your own crystal ball prediction, mine is 10x)
Best of luck with your investments!
AmerisourceBergen / Strategic Commercialization Agreement for ONS-5010 for the Treatment of Wet AMD
OTLK is getting some commercial muscle once market approval is in:
ISELIN, N.J. and CONSHOHOCKEN, Pa., Sept. 27, 2022 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a pre-commercial biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, and AmerisourceBergen (NYSE: ABC), a global healthcare company and leader in specialty pharmaceutical distribution and services, announced today that they have entered into a strategic relationship in preparation for the anticipated commercial launch in the United States of ONS-5010 / LYTENAVA™ (bevacizumab-vikg), if approved by the U.S. Food and Drug Administration (FDA).
AmerisourceBergen will provide third-party logistics (3PL) services and distribution, as well as medical information and pharmacovigilance services in the United States. As Outlook Therapeutics moves toward a potential launch in the United States, and if ONS-5010 is approved by FDA, AmerisourceBergen’s commercialization support will expand to include additional services, such as patient services and field solutions.
“Following our recent Biologics License Application (BLA) submission, entering a relationship with AmerisourceBergen for ONS-5010 is a critical step in the next phase of our pre-commercial strategy execution,” commented C. Russell Trenary, III, President and CEO of Outlook Therapeutics. “AmerisourceBergen is the preeminent leader in specialty pharma distribution, which will provide expansive reach and access to the vast majority of anti-VEGF providers. This is expected to significantly enhance our commercial reach. Together, we believe we will be in a position to significantly upgrade treatment options for people living with wet AMD.”
“We are thrilled to support Outlook Therapeutics for their pre-commercial launch preparations and, pending FDA approval, plan to leverage our portfolio of commercialization solutions to help them maximize commercial success and increase patient access,” said Willis Chandler, President of Global Pharma Services at AmerisourceBergen. “We are uniquely positioned to deliver support across the product lifecycle to meet our partners’ specific needs and help them achieve the outcomes they desire. We look forward to continuing to expand our support—both in the U.S. and key markets worldwide—over time.”
As the exclusive distribution partner to more than 65,000 community practices nationwide, AmerisourceBergen distributes specialty care products to community practices, such as retinal, eye surgery and ophthalmology practices. If ONS-5010 receives approval, AmerisourceBergen’s Besse Medical, one of the largest specialty pharmaceutical distributors to retina specialists, will work to ensure providers across the United States have efficient access to the product. As part of the agreement, AmerisourceBergen’s ICS affiliate, a leader in outsourced logistics and distribution services, will provide distribution support, including cold chain storage, via its network of facilities nationwide. Innomar Strategies, a leading service provider for biopharma companies in Canada and a part of AmerisourceBergen, will deliver pharmacovigilance and medical information services for ONS-5010 in the United States.
Through the agreement with AmerisourceBergen, Outlook Therapeutics expects to significantly increase market access and efficient distribution of ONS-5010, if approved by the FDA. Moreover, working with AmerisourceBergen will help to provide Outlook Therapeutics with an accelerated pathway to deliver a high-quality customer experience to retina specialists.
Outlook Therapeutics is also exploring a relationship with AmerisourceBergen to support the launch of ONS-5010 in international markets. AmerisourceBergen expanded its global distribution capabilities in 2021 with the acquisition of Alliance Healthcare, a leading wholesaler of healthcare products in Europe.
SA Reference Article
A good summary of the investment thesis around CYRX as a growth company. It's a clear article, well organized, simple to read.
It captures why I invested in CYRX and why this is a medium/long term opportunity.
https://seekingalpha.com/article/4542593-cryoport-a-rare-investing-opportunity
The article goes over:
* An overview of the Company
* The Investment Thesis
* The industry Tailwinds
* EMEA Expansion - Belgium With Cell Matters Acquisition
* EMEA Expansion - Spain With Polar Express
* EMEA Expansion - France With Cell & Co BioServices
* Strategic Partnership With Takeda
* Operational Performance - Robust Expansion In All Business Segments
* Operational Performance - Supporting More Clinical Trials
* Competitor Landscape
* Financial Assessment
* Valuation Analysis
* Shares Repurchase Program
* Potential Risks
* Conclusion
Conclusion
In all, I maintain my buy recommendation on Cryoport with a 5/5 stars rating. Cryoport is a rare investment opportunity because it is profiting from the strong industry tailwind favoring cellular therapy innovators. So long as the cellular therapy sector continues to grow, leading companies like Cryoport (and BioLife) will enjoy more business, thus continuing to ramp up their topline growth. Over the years, the company would then bank a profit due to the economy of scale.
As it leverages growth with the sophisticated M/A approach, Cryoport can grow much faster than other firms. Over the years, Cryoport has been quite busy with making additive acquisitions. 2022 alone witnessed three significant buyouts - Cell&Co, Polar Expres, and Cell Matters. Then, there's the Takeda partnership.
Despite such strong growth, Cryoport is still a young company with substantial upsides. By purchasing shares in such a firm and holding it for many years, you can earn multi-bagger profits.
CYRX down in the last couple of weeks, without any substantive news.
Staying long.
Best of luck with your investments!
Houston again, partnering with Takeda's BioLife Plasma Services
The Houston location will help the partnership synergy.
Cryoport Enters into Strategic Relationship with Takeda's BioLife Plasma Services
Cryoport plans to establish an integrated supply chain platform with BioLife Plasma Services to offer standardized cell therapy collection, processing, and storage services in United States and Europe over time
NASHVILLE, Tenn., Sept. 8, 2022 /PRNewswire/ -- Cryoport, Inc. (Nasdaq: CYRX) ("Cryoport" or the "Company"), a global leader in temperature-controlled supply chain solutions for the life sciences industry, today announced it has entered into a strategic relationship with BioLife Plasma Services, part of the global biopharmaceutical company Takeda, intended to provide consistent, high-quality cellular starting material for use in the manufacture of life-saving cellular therapies.
By bringing together BioLife Plasma Services' proficiency in apheresis collection and their donation center infrastructure with Cryoport's life sciences' world-class capabilities and expertise in temperature-controlled supply chain solutions for the biopharmaceutical industry, the companies aim to establish a standardized, integrated apheresis collection, processing, and distribution solution for cellular therapies. Importantly, the new platform will leverage the cryo-processing expertise of Cell Matters, which Cryoport acquired in late July 2022.
Nearly 4-year median overall survival benefit in the radiation-only group
Yep, not too shabby.
To clear up any doubt about pre-specification, I will quote the protocol for you:
“ Additional analyses will be performed for the risk group assignment and for the type of therapy administered (radiotherapy, concurrent chemoradiotherapy) following surgery. The major prognostic factor for the subjects is the assignment to either the ‘high risk’ or ‘low risk’ group….”
We did this because it was obvious that there might be different outcomes for the risk groups, since they received different treatments. That is why the protocol said that risk group assignment was “ the major prognostic factor .” FDA and 23 other regulators around the world reviewed this protocol and allowed the study to proceed. The statistical analysis plan (SAP), which was finalized while we were blinded to the data, has the same pre-specification as the protocol.
There has been confusion from some critics who suggest that because the radiation-only group was a “subgroup,” the analysis of that group is meaningless. Although some subgroups can be meaningless when they are analyzed after reviewing the data, are not pre-specified, have a small sample size, and lack a biological reason, our analysis was done before we saw the data, it was pre-specified, has a large sample size, and has a biological reason, among other supportive aspects. We also rely on more than just a subgroup. The responder survival benefit was seen in the total Multikine population, where the death rate was 22% for responders compared to 54% for non-responders. The hazard ratio was 0.3, which means that responders lived about three times longer than non-responders, and this benefit was very statistically significant (p<0.0001).
We have met with FDA and have received their questions and comments. This is normal. We plan to submit a major follow-up package to FDA soon that will address those questions and comments. At about the same time, we plan to file the Clinical Study Report, which is typically filed with a biologics license application (BLA).
For those who ask “what is taking so long,” please keep in mind that we have done what no one else has done before . The last FDA approval for previously-untreated advanced primary head and neck cancer was decades ago. Our treatment is novel, and our data is extensive and solid. We can identify with high accuracy the patients who are most likely to have great overall survival benefit from Multikine, over 200,000 patients per year globally. We believe FDA and other regulatory agencies will recognize these patients’ dire need for a treatment better than what is available today. In addition, we continue to validate our manufacturing facility to ensure that we will be in compliance with the standards for BLA approval.
Bought another slice at $1.09! The MC is < $250M!!
I would believe the MC will largely exceed $250M post approval, a very likely event.
Best of luck with your investments!
Thanks DavidW2
I must say they are an exception in the biotech world. They hit their target dates pretty much every time. And they exceeded expectations on this one.
https://ir.outlooktherapeutics.com/news-releases/news-release-details/outlook-therapeuticsr-re-submits-biologics-license-application
ISELIN, N.J., Aug. 30, 2022 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, today announced it has re-submitted its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ONS-5010, an investigational ophthalmic therapy which, if approved, will be branded as LYTENAVA™ (bevacizumab-vikg) for the treatment of wet age-related macular degeneration (wet AMD).
“Over the past three months, we have worked diligently to provide the additional required information that was not included in our March 2022 BLA submission, to address requests from the Agency to ensure our BLA is complete for acceptance and review. We believe that this re-submission addresses each of the comments and recommendations from the Agency, and we are confident in the revised BLA application,” said Russell Trenary, President and CEO of Outlook Therapeutics. “We remain committed to bringing ophthalmic bevacizumab to market, which if approved, can provide retina patients with an on-label treatment option that helps patients avoid the health risks associated with unapproved repackaged oncologic IV bevacizumab.”
“Our NORSE TWO pivotal trial for ONS-5010 showed compelling efficacy and clinical relevance coupled with a robust safety profile, and we are confident that our investigational drug, if approved, will be a valuable therapeutic option to treat retina diseases,” added Terry Dagnon, Chief Operations Officer of Outlook Therapeutics. “ONS-5010 is designed and manufactured to be fully compliant with FDA’s criteria for ophthalmic biologics to meet the public health need for an FDA-approved ophthalmic formulation of bevacizumab.”
In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics has continued its commercial launch planning. These activities include establishing best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Ajinomoto Bio-pharma Services for finished drug product. Outlook Therapeutics is also actively building out its distribution and commercial capabilities.
101.7 month vs.. 55.2 months mOS
Rather impressive.
? 101.7 months median overall survival in the lower risk Multikine treatment cohort vs. 55.2 months for standard of care;
? 16.0% early response rate for Multikine vs. 0% for standard of care;
? 17.6% death rate for early responders in the lower-risk treatment cohort vs. 42.7% for non-responders;
? Progression free survival presents a 0.76 hazard ratio;
? Overall survival presents a 0.68 hazard ratio.
? 16.0% early response rate for Multikine vs. 0% for standard of care;
? 17.6% death rate for early responders in the lower-risk treatment cohort vs. 42.7% for non-responders;
? Progression free survival presents a 0.76 hazard ratio;
? Overall survival presents a 0.68 hazard ratio.
Benzinga Article
https://www.benzinga.com/markets/penny-stocks/22/08/28663723/cvm-clinicaltrials-submission
A good recap of the situation, the basic trial data, and the next steps, including:
CEL-SCI Milestones
? Submission of data of clinicaltrials.gov – May 2022
? Presentation of abstract at ASCO – June 2022
? Appointment of Gail Naughton to Board of Directors – August 2022
? Development of clinical study report – 2022
? Request meeting with FDA to determine path forward – 2022
? Development of paper(s) for publication in peer reviewed journal – 2022
? Presentation of data package to review with FDA – 2022
? Address FDA Comments – 2022
? Submission of BLA to FDA – 2022
Bought another slice at $1.14
September coming soon to a calendar near you.
Best of luck with your investments!
NWBO End Game Chess Moves
1) NWBO does not sit on their hands, that's for sure. After Manufacturing, they are getting their ducks lined up for MHRA, and they submitted the PIP back in Feb. 22. That takes work to put that together and get it through the regulatory process.
The Company submitted its proposed PIP to the MHRA in February 2022, and has been going through the regulatory review process since then. On August 17, the Company received final approval of the PIP from the MHRA.
The final regulatory approval of the PIP must be obtained before a sponsor may submit a Marketing Authorization Application (MAA) for approval to commercialize the new medicine for adult patients.
Northwest Biotherapeutics worked with expert consultants for months to develop a PIP tailored for application of DCVax-L to pediatric cases of HGG.
Yes, that was indeed the sense of my posting the Company's paragraph.
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Pre-specified in the original study protocol and in the SAP.
Analysis of the lower-risk-for-recurrence arm was pre-specified in the original study protocol and in the statistical analysis plan. This arm comprised about 40% of all study participants.
14.1% absolute OS advantage at 5-years in the lower-risk-for-recurrence arm (62.7% vs 48.6%) for Multikine+CIZ patients versus SOC patients. OS benefit was also shown at 1, 2, 3, and 4 years.
Nearly 4-year increase in median overall survival in the lower-risk-for-recurrence arm (101.7 months for Multikine+CIZ versus 55.2 months for the SOC).
Histopathological analysis confirmed the effect of Multikine, as 61 markers, ratios, and combinations showed a statistically significant effect in the lower-risk-for-recurrence arm (two-sided p<0.05) favoring Multikine+CIZ versus the SOC for OS, progression free survival, and loco-regional control outcomes.
Additional (confirmatory) progression-free survival benefit in the lower-risk-for-recurrence arm was observed for Multikine+CIZ versus the SOC.
No excess safety issues : The overall incidence of adverse events and serious adverse events in the Multikine arms was not substantially different versus the SOC.
Furthermore, because it was obvious when the study was designed that Multikine might provide a benefit in only one of the two SOC risk groups, CEL-SCI pre-specified in its original study protocol that analyses of the trial results should take place for all, as well as for each of these groups. Separate analyses of the lower-risk-for-recurrence and higher-risk-for-recurrence treatment arms were also pre-specified in the study’s statistical analysis plan which was completed before data lock and the study result were analyzed.
IT-MATTERS Phase 3 Trial Results Summary
This release summarizes the results recently posted on clinicaltrials.gov for the overall ITT population as well as the subjects constituting the Proposed Indication representing 41.2% of the study overall ITT population. ( See https://clinicaltrials.gov/ct2/show/results/NCT01265849?term=multikine&draw=2&rank=2 ) Please refer to the clinicaltrials.gov presentation of the data for further information on study design and study data.
Objective Responses Before Surgery (partial and complete tumor response per RECIST, confirmed at surgery by pathology) : In the overall ITT population, objective responses before surgery (sometimes also called “early responses”) were observed in 45 subjects who received Multikine for 3 weeks; no such responses were observed in the SOC alone (control) (p<0.00000001).
Five subjects who received Multikine+CIZ had complete tumor responses confirmed at surgery.
In the overall ITT population (n=923), objective responses were seen in:
8.5% of Multikine-treated subjects (45/529).
8.1% of the Multikine+CIZ treatment arm (32/395).
9.7% of the Multikine without CIZ treatment arm (13/134);
0% of the SOC alone (control) treatment arm (0/394).
In the Proposed Indication (n=380), objective responses were seen in:
16.0% of Multikine-treated subjects (34/212).
15.2% of the Multikine+CIZ treatment arm (24/158).
18.5% of the Multikine without CIZ treatment arm (10/54); and
0% of the SOC alone (control) treatment arm (0/168).
Objective Responses Before Surgery Were Prognostic For Survival with a Significant Decrease in Death Rate:
In the overall ITT population (n=923), the 22.2% death rate among Multikine objective responders before surgery (n=45) was significantly lower (two-sided Fisher Exact test p<0.0001; HR=0.301) than the 54.1% death rate for the remaining Multikine non-responders (n=484);
In the Proposed Indication (n=380):
the 17.6% death rate among all Multikine objective responders before surgery (n=34) was significantly lower (two-sided Fisher Exact test p=0.0067; HR=0.348) than the 42.7% death rate for the remaining Multikine non-responders (n=178).
the 12.5% death rate among Multikine+CIZ objective responders before surgery (n=24) was significantly lower (two-sided Fisher Exact test p=0.0101; HR=0.246) than the 41.0% death rate for the remaining Multikine non-responders (n=134).
Significant OS advantage in the Proposed Indication for the Multikine+CIZ treatment arm versus the SOC control:
5-year absolute OS advantage of 14.1% (62.7% vs 48.6%);
proportional hazards two-sided p=0.0236;
0.68 hazard ratio equating to a 47% OS prolongation; and
3-year and 4-year absolute OS advantage of 4.9% and 9.5%, respectively, are supportive.
In the overall ITT population, no statistically significant OS difference was seen between the two main comparator groups (proportional hazards two-sided p=0.4128). It is believed that the higher-risk-for-recurrence patients in the overall ITT were too sick to tolerate the extra three-weeks before surgery for the Multikine treatment and also that chemotherapy may impair Multikine’s immunological mechanism of action.
Nearly Four-Year Median OS Benefit : In the Proposed Indication, the median OS for those receiving Multikine+CIZ was 101.7 months versus 55.2 months for the control, a survival improvement of almost four years. The Multikine treatment arm without CIZ in the Proposed Indication also had better median OS than control (68.2 months vs. 55.2 months).
Progression-Free Survival (PFS) : In the Proposed Indication, there was confirmatory PFS difference between the two main comparator groups (HR=0.76; proportional hazards two-sided p=0.0896). In the overall ITT population, there was no statistically significant PFS difference between the two main comparator groups (proportional hazards two-sided p=0.3728).
Locoregional Control (LRC) : In the Proposed Indication, there was no statistically significant LRC difference between the two main study groups (proportional hazards two-sided p=0.4082). In the overall ITT population, there was no statistically significant LRC difference between the two main comparator groups (proportional hazards two-sided p=0.8020).
Significant Histopathological Results : OS, PFS, and LRC were examined using a proportional hazards model to assess the interactions between histopathology (HP) cellular marker expression levels, risk group (lower and higher), and treatment in the two main comparator groups. Twenty HP markers were classified as low, medium, and high. Two HP ratios were classified as low, medium, and high. Fourteen HP combinations were classified as low and high. These resulted in 94 possible comparisons for each of OS, PFS, and LRC.
Significance favoring Multikine+CIZ vs. control (two-sided p<0.05) was observed in the Proposed Indication as follows:
OS: 14 markers, 2 ratios, and 9 combinations;
PFS: 11 markers, 1 ratio, and 5 combinations;
LRC: 9 markers, 1 ratio, and 6 combinations;
Combined (summed across endpoints), significance was reached for 21.6% (61/282) of the total possible comparisons, and the one-sided 97.5% confidence bound on the fraction significance was 16.3% which exceeds 5% chance alone.
No excess safety issues:
The overall adverse event rates were 92.4% for the Multikine+CIZ treatment arm; 95.9% for the treatment arm receiving Multikine without CIZ, and 96.1% for the SOC alone (control) treatment arm.
The overall serious adverse event rates were 53% for the Multikine+CIZ treatment arm, 50.7% for the treatment arm receiving Multikine without CIZ, and 52.7% for the SOC alone (control) treatment arm.
The incidence of adverse events and serious adverse events noted in the Multikine arms was not substantially different from those in control.
Results Submittal Timeline and Expectation
Here is the timeline of results submittal and how long it took each time for CVM to respond:
It went from a few weeks to a couple of weeks to around a week to now the same day.
I think they fixed the last remaining issues and the Aug 17th rejection was due to minor details. I think this is the last submittal before the OK and the result publication on https://clinicaltrials.gov/ct2/show/results/NCT01265849?cond=NCT01265849&draw=2&rank=1&view=results
The time for that OK may still be one month. So my expectations is that around Sept. 17th (that being a Saturday), we will have the results published.
Best of luck with your investments!