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My bad on post a few weeks ago. When I posted about $MRNA cash position, I didn't do the research I should have done and used what was on cash flow statement and didn't look into long term investments, very sloppy of me. Sorry about that.
In today's release, they are projecting to use $4.3 billion of their cash plus investments during 2024. At 12/31/23 they reported cash plus LT investments of $13.3 billion and project about $9 billion at end of 2024. It will take longer than I thought for them to run out of cash and hopefully $ABUS takes a huge chunk of it. Today MRNA had a surprise profit, and I am still hoping that $ABUS finally cleans their clock for their blatant theft of IP.
Handle on twitter is @DesertDweller93
I've been saying on X for a month or so that $MRNA will be suffering a drop once it becomes known that they have roughly a year's worth of cash left, I just discovered this recently. They are burning almost $7 billion/year and they will report less than that at 12/31/23. That on top of the fact that during the past 3 years, they spent $7 billion in buybacks at prices much higher than current prices, all the way up to $300+. My prediction is major restructuring or significant secondary very soon. I bet they wish they had that cash now instead of overpriced treasury stock but then mgt wouldn't have been able to sell at those inflated covid prices.
Hope $ABUS puts them into bankruptcy, the f'n thieves and I hope ABUS cleans $PFE and Biontech's clock too. They all know they are stealing the tech and just don't care. About time David kicks Goliath's ass again.
I used to own a substantial number of shares and got out a long time ago of most of my shares, only hold a token amount now. For all the old timers here, I really hope that IDCC finally goes for the jugular and makes someone pay BIG. Their history has always been to settle on the courthouse steps. I hope this time is different and all longs finally get the reward you deserve. These scumbag thieves need to pay up once and for all and make everyone else afraid to steal from them. Good luck.
Sorry for the lengthy post but I believe this is critical to my investment in PDS and it’s complicated but worth your time. Some of what is discussed below are facts that have been presented by the company or NCI followed by my interpretation/guess as to what it means. After you read this, you will understand why I am so excited about PDS potential, and why I believe the street is missing something incredible and why it is my largest investment.
In June 2021 we learned that 16 out of 18 HPV16++ patients were still alive at 8 months, an incredible outcome in such a difficult to treat group. This included 10/12 CPI refractory patients who are among the sickest patient population with a life expectancy of 3-4 months with current standard of care. The other 6 patients were CPI Naïve patients with a life expectancy of 7-11 months using current SoC and all of whom were still alive at 8 months. The NCI treated 7 HPV16 negative patients who did not meet the criteria for objective response, so they decided to stop treating this group. In summary, in June 2021 they reported on a total of 25 patients who were treated with the combo, 18 who are the targeted population and 7 who are not.
Last week we learned that among 37 evaluable patients (more on this below) the median survival was >12-months at 12/31/21. This is incredible when you look at the overall survival in current standard of care in this population group. Yesterday I received confirmation that the 37 patients included the 7 “off-target” HPV16 negative patients. Median means that half the patients are above a particular number and half are below. That would mean that median survival means half the patients (19) in this population survived for more than 12 months, and the other half (18) have not YET survived for at least 12 months.
At this point we don’t have the details that will come later in the year, but I believe we can infer some very important information. Here is where my speculation and interpretation of the data comes in. Please let me know if I am missing anything or not interpreting the data correctly.
The 37 evaluable patients include patients who have been treated with the combo therapy AND who have received the necessary scans to be considered evaluable, not necessarily that they were in the trial for more than 12 months at 12/31/21. This means it includes patients who were treated in 2020 AND patients who were first enrolled and treated in 2021. This is an important point to remember. Some of those who were treated and considered evaluable haven’t been in the trial for 12 months at 12/31/21 and still 19 out of 37 evaluable patients survived for more than 12 months. Think about how incredible that is but it gets even better.
When the full dataset comes out and we see the details, I believe that the >12-month survival milestone will be achieved by way more than 50% of those treated. I come to this conclusion based on the 37 patients included as evaluable. We know 7 evaluable patients were HPV16 negative. Those patients didn’t have Objective Responses to the treatment based on ASCO data and new enrollment was stopped as a result. I think since they didn’t respond we can unfortunately assume most of them did not achieve the 12-month survival milestone. This would leave 30 targeted patients included in the 37 evaluable. Remember, some of the 30 remaining were considered evaluable because they received treatment and had required scans but were first treated during 2021.
How many were first treated during 2021 and therefore couldn’t be included in the >12-month survival median? We know from ASCO that there were 18 on target patients treated for 8 months as of May 2021, meaning they were treated before 10/2020, 8 months before data cutoff for the presentation. We also know 16 out of these 18 were alive for at least 8 months and counting per ASCO.
There are 12 patients remaining in the target group (30 minus 18) that we don’t know when they were first treated. Even if we assume 1 per month for 12 months beginning 10/2020 forward, it means there were 3 patients treated in 2020 with the remaining 9 treated in 2021. If this assumption is close, that would mean that out of the 37 evaluable patients, 9 were treated in 2021 leaving 28 patients who were in the trial prior to 12/31/20.
We know 19 patients survived for more than 12 months per the HC Wainwright update where the median survival was greater than 12 months. If 19 out of 28 treated in 2020 survived for more than 12 months and 7 of the 28 were HPV16 negative, how incredible is that? Now assume most, if not all the HPV negative patients did not survive for >12 months, it would mean close to 19 out of 21 targeted patients achieved the >12-month survival milestone.
We know from the trial design that there will be 36 CPI refractory patients and 20 CPI naïve patients in the trial. The life expectancy of the refractory population is 3-4 months, and the life expectance of the naïve patients is 7-11 months. What is a reasonable assumption for the blended life expectancy of the treated group? Since there are more patients in the refractory population, using a blended average life expectancy of 5-6 months to compare to the median of > 12-months (and possibly growing) shows just how incredible the results are. This is what the street is missing.
This trial is in a very hard to treat population with a very high unmet need. When this trial completes and the data are available, how long will it take for the NCI to have meetings with the FDA for accelerated approval based on the study assuming the full data are as good as what we have seen to date? What would be a reasonable assumption for approval and more importantly, revenue coming into PDS? How is this trading at a market cap of less than a billion right now? What am I missing?
How do you like this portion?
Moderna, BioNTech and Pfizer are on their way to selling $45 billion worth of vaccines in 2021. They don’t pay a dime to MacLachlan. Other coronavirus vaccine makers, such as Gritstone Oncology, have recently licensed MacLachlan’s Protiva-Tekmira delivery technology for between 5% and 15% of product sales. MacLachlan no longer has a financial stake in the technology, but a similar royalty on the Moderna and Pfizer-BioNTech vaccines could yield as much as $6.75 billion in 2021 alone. In an ironic twist of fate, though, President Biden’s proposal to waive Covid-19 vaccine patents would make it unlikely that the intellectual property related to MacLachlan’s advances could be a source of riches.
Covid’s Forgotten Hero: The Untold Story Of The Scientist Whose Breakthrough Made The Vaccines Possible
Link to Forbes article
You are getting ahead of yourself, PDS is ONLY up 400% YTD, not 700%. Give it time, we will soon be saying much higher than 700%, just not yet.
So happy to see you were away having fun and buying a house in paradise, congrats. When you went silent, I was concerned. Now that you are back, how about making PDS jump to $15 by this Friday and $30-40 by next Friday?
I resemble that remark.
"I haven’t sold one share of my position which is probably foolish but to many extraordinary things ahead."
It is my #1 investment, now by a significant margin, and I only began investing in it last August. I exercised some options last week at $7.50 and I plan on selling those shares by next Friday, just to be safe. I had no intention of buying those shares, I just couldn't sell the underlying option with what I think I see. I figured I would make far more by exercising the expiring option at $7.50 then selling the stock later. I thought I would sell Monday but I am greedy and decided to hold, glad I did.
After I sell those shares, my next sale will be at $20 to get my investment out then let the rest ride, hopefully to triple digits within a year or so. Depending on the presentation in a week and a half, this could go parobolic. So little institutional ownership, <15% as of 03/31/21, which will cause an explosion after the Oral presentation if the data are as good as preliminary. I can't imagine the data will be worse and I think it will only be better. Unreal how high I think this could go with the right following in a short time frame.
Too bad Fress isn't around. Hope he is OK.
Am I crazy in thinking PDS or one of its bigger, better funded partners like the NCI, GlaxoSmithKline or Merck KGaA could be having discussions right now with FDA and other regulatory bodies about modifying the current P2 and having it changed to an Accelerated Approval Trial? I think all agree that the preliminary results were nothing short of amazing with an overall response rate of 71% in an indication that current Standard of Care (SoC) runs only about 20% response rate, at best.
To my knowledge, accelerated approval is warranted when an experimental treatment demonstrates positive results where either no current SoC exists or where the treatment is clearly better than SoC in an underserved population. Approval also needs to be based on an acceptable safety profile. Assuming the data at ASCO build upon the early results, why would they not modify the trial so approval could come as early as next year?
For reference, I have been invested in SGEN for about 10 years. From memory, I believe their first drug, Adcentris, was approved based on an accelerated trial with only 100 patients. After approval, they needed to perform follow up P3 trials to confirm the P2 trial. What would be stopping the NCI from following the same path?
I understand it will take time to get through the red tape, but after the data are presented at ASCO, think/dream about where the market cap would be if in 3 months PDS announced the current trial was changed to an Accelerated Approval trial. I believe the market cap would easily be in the $3-5 billion range shortly after such an announcement. Upon approval, which could come as early as late 2022 or early 2023, that could easily double the market cap.
While some may think I am certifiable suggesting a possible triple digit price this year, remember there are currently only 23 million shares outstanding. The above scenario easily translates into triple digits and possibly mid triple digits in just a few short years. Obviously, all predicated on an accelerated approval, but I do not see why this is not just possible but likely if ASCO shows the same or better results.
I know I have been predicting triple digit prices for PDS for the past few months. What would a reasonable market cap be for a company that could be in the middle of a registrational trial with an addressable market of tens or possibly hundreds of thousands of patients? I know I am dreaming that it’s possible, but with results seen to date, can anyone tell me why PDS, Glaxo, Merk KGaA, or the NCI would not be trying to get this combo trial to market much sooner under accelerated status?
Comments and corrections are welcome.
Every investor has their own time horizons and risk tolerances. Taking profits isn't a bad thing but the thing you don't want to do is sell too soon with a company that has so much explosive growth potential IF THE DATA continues to show proof of concept.
For me, last week's unbelievably impressive results removed a lot of risk as I believe it demonstrates Proof of Concept. Assuming it shows similar or better results in 2 weeks, followed later this year with Keytruda combo and MD Anderson trials, today's price could be the buy of the decade.
IF, and I say IF, the data demonstrates PoC with the other 2 trials, there is no reason a $5 billion and higher market cap isn't possible and is likely imo. Throw in possible Covid approval and a $5 billion market cap will be small in 6-12 months. I know a lot has to go PDS way, but last week's data was huge. With current share count less than 23 million, dream about what a $5 billion market cap translates to, sounds CRAZY, but it is possible.
No stock can go straight up but even after the great run, PDS market cap is still only about $175 million, extremely small given its potential. This could double from here and still be low valued.
Since we know in exactly 2 weeks we get updated data on the unbelievably impressive results last week, I can see a situation were we continue in a very strong uptrend, possibly doubling from here. Where we go after ASCO presentation and the company's cc will depend on the data.
Will they report even more impressive data when you add another 10 or so patients? Does some respected bio journalist "find" PDS and report on the data?
So many things that could get this to a half billion and more market cap in the near term. We are just getting started imo. Fingers crossed.
PDS should start moving early if we get some press coverage about today's impressive results. The company will most likely issue a PR early and hopefully that gets it to catch fire and start moving towards double digits where we belong.
I sent an email to Allison Gatlin at IBD telling her about today's abstract and suggesting she right a story about PDS. She and I had exchanged emails in the past concerning my current #1 investment, UniQure after she wrote a story about them. I don't expect UniQure to hold that position for much longer as I expect PDS to rise significantly over the coming days and weeks. I am still very optimistic about qure long term but I think pds moves much more rapidly. I am hoping she looks into PDS and writes an article to gain some momentum.
The company should get positive press from the abstract if the journalists are aware of it. Since it is such a small company that is not followed by many analysts, I wouldn't be surprised to see this go under the radar until ASCO presentation. Hope it catches fire tomorrow and Friday as my options need a run over $7.50 to be in the money :^) Can't believe it didn't close over that price in AH's today.
Congrats to all. PDS will be one of the best investments of 2021 imo.
I couldn't agree with you more about this being the most undervalued company of 2021. If you read my posts here and over on Twitter, you will see I have been a firm believer in it ever since I noticed @Pharmdca on Twitter recommend it in late 2020. He was in it before then, I just didn't know until then. The more I researched it, the more impressed I became. Today's news reduces the risk immensely for me and it will open tomorrow as my 2nd largest holding after taking the #2 spot from tril. Before long, I believe it will be my #1 holding.
Check out the current, updated corporate presentation linked below. They parse out the data and it is unbelievably impressive in this hard to treat cancer. Assuming the rest of the trial shows similar efficacy, I bet this gets Accelerated Approval based on this P2 trial since there are no good treatment options available.
Current Corporate Presentation
When telling friends and family about PDS potential, I always explain how I know it sounds crazy to be suggesting a possible triple digit price for a company currently trading at mid single digits but that is the potential for PDS, if it stays independent long enough. I believe positive data on the Keytruda trial and this gets bought out by Merk (or someone else) for some ridiculous price imo.
GLTA, hope the data continues to show this kind of efficacy for us investors and more importantly for the patients. The hope these type of results can offer those suffering are incredible and I hope it continues to work.
Fress hasn't posted on IH since 05/05/21 regarding any stock. I hope he is OK. He has been the biggest bull on PDS (other than maybe me :^) and it is odd that he has been silent with the upcoming data tomorrow.
Quarterly cc definitely got me more excited about tomorrow's abstract and I think we could be the talk of the financial community if the data is strong. Market cap slightly above $100 million currently. This could easily triple or more on the news and still be low priced compared with others. How many small bio's have 3 P2 trials w data to be released within 6-9 months on all 3? Positive data on any of them and it is Proof of Concept for entire platform. What will that be worth as an independent company and what will it be worth to big (and not so big) pharma? It could be swallowed up for a billion or two which would be great returns from these levels and barely dent big pharma's balance sheet.
Hoping the data is great tomorrow. Remember current standard of care results in only 20% response rate. Best clinical drug that is being combined with Versamune is 30%. We know trial resulted in at least 40% response rate in first <8 patients treated. Tomorrow should present on 20-25 patients according to cc. If we are able to present response rates at 50% or higher in heavily pretreated population, what does that do to stock price and market cap?
Could be a very explosive end of week. GLTA and here's to hoping for blockbuster data.
Where is Fress? He sure has been quiet lately. Hope all is ok.
Wednesday could be the most important day in the history of the company. Based on the way I interpreted the quarterly cc, I think we will get market moving data and that is the reason I took a crypto like bet and so far bought 98 $7.50 05/21/21 calls. I had a buy for 130 contracts but so far only 98 have filled.
If they release proof of concept data with the ASCO abstracts, there is no reason for the stock not to hit $200-400 million market cap shortly after. IF, and I say IF, that were to happen we would be looking at almost $10-20/share. How cool would that be buying calls for a nickel that go up by that magnitude? Never happened to me before but keeping fingers crossed it happens this week. Best of all, they are in a Roth IRA :^)
Barring a total disappointment Wednesday, long term PDSB is such a screaming buy at these levels. Can't believe the M.C. is where it's at, CRAZY.
Good luck to all and have a great weekend. Only a few days to find out if we are idiots or geniuses, that is if the abstract shows data.
Crazy how relatively quiet this board is so close to ASCO abstract release. In 6 short (or long like a kid waiting for Christmas) days, we will get our best peek yet to see if our belief is warranted and whether or not PDSB will make us significantly wealthier than we are today. Place your bets accordingly.
Here is a link to the cc transcript today.
Seeking Alpha CC transcript
PDS Biotechnology Corp (NASDAQ:PDSB) Q1 2021 Earnings Conference Call May 13, 2021 8:00 AM ET
Company Participants
Deanne Randolph - VP, Commericial Development & Head, IR
Frank Bedu-Addo - President, CEO & Director
Lauren Wood - Chief Medical Officer
Seth Van Voorhees - CFO, Principal Financial & Accounting Officer
Conference Call Participants
Joseph Pantginis - H.C. Wainwright & Co.
Leland Gershell - Oppenheimer
Operator
Hello, and welcome to the PDS Biotechnology First Quarter 2021 Earnings Call and Webcast. [Operator Instructions].
As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Deanne Randolph. Please go ahead.
Deanne Randolph
Good morning, and welcome to PDS Biotechnology's First Quarter 2021 Earnings Conference Call and Audio Webcast. With me today are Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Lauren B. Wood, Chief Medical Officer; and Dr. Seth Van Voorhees, Chief Financial Officer. Earlier this morning, PDS Biotech issued a press release announcing financial results for the quarter ended March 31, 2021. We encourage everyone to read the press release as well as PDS Biotech's quarterly report on Form 10-Q, which will be filed with the SEC later today. The company's press release is available on PDS Biotech's website at pdsbiotech.com, and the quarterly report will be posted later today. In addition, this conference call is being webcast through the company's website and will be archived there for future reference.
Before we begin, I would like to caution listeners that comments made by management during this conference call will include forward-looking statements within the meaning of federal securities laws, including the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve material risks and uncertainties, and the company's actual results may differ materially.
For a discussion of these risk factors, including, among others, the risks related to COVID-19, the impact such pandemic may have on the company's business operations, financial operations and results of operations and the company's ability to respond to the related challenges, including those noted in this morning's press release, please refer to PDS Biotech's SEC filings. Investors, potential investors and other listeners are urged to consider these factors carefully in evaluating the forward-looking statements and are cautioned not to place undue reliance on such forward-looking statements.
Please note that the content of this conference call contains time-sensitive information that is accurate only as of the date of the live broadcast, May 13, 2021. Except as required by law, the company undertakes no obligation to revise or update any statement to reflect events or circumstances that take place after the date of this call. Following today's prepared remarks, we will open the discussion for a question-and-answer session. With that, I would now like to turn the call over to Dr. Frank Bedu-Addo. Frank?
Frank Bedu-Addo
Thank you, Deanne, and thanks to everyone on the call today. 2021 has so far been an exciting year for PDS Biotech. The company has continued to advance clinical development of our Versamune-based immuno-oncology pipeline through key initiatives and we are making significant progress with our clinical trials. Since we last spoke to you on our fourth quarter call, we have made further progress with our ongoing Phase II clinical trials as well as with our preclinical pipeline products. Our lead oncology candidate, PDS0101, as you may recall, is currently being studied in 3 Phase II clinical trials in advanced HPV-associated cancer.
The most advanced of these trials is a National Cancer Institute-led study evaluating a novel triple immunotherapeutic combination of PDS0101 with 2 of MD Serono clinical-stage immunotherapies, bintrafusp alfa or M7824, which is a bifunctional checkpoint inhibitor and NHS IL-12 or M9241, which is an immuno cytokine. This triple combination is being evaluated in HPV16 positive relapsed or refractory advanced HPV-associated cancers. And these include anal, cervical, head and neck, vaginal and vulva cancers. This population is a well-documented and difficult-to-treat patient population in which more refractive therapies are desperately needed.
In January, we announced that this National Cancer Institute-led trial have achieved its preliminary efficacy benchmark with 3 or more of the first 8 patients, which approximates at least 40% achieving tumor regression. This benchmark represents a doubling of the response rates seen in this population of refractory patients with standard-of-care checkpoint inhibitors and at least a 30% increase over the results reported with the most promising experimental agents in this population to date, which is bintrafusp alfa. As a result of the significant preliminary efficacy achievement, a second arm was opened up to study the combination in refractory HPV16 positive patients who have, in addition, also failed treatment with checkpoint inhibitors. In this population, who have few options, the treatment response rate is only about 10%, with a medium survival time of about 3 to 4 months.
A few weeks ago, we announced that more mature interim data from this triple combination trial has been accepted for oral presentation on June 7 of the 2021 American Society of Clinical Oncology, also known as ASCO, annual meeting. As you may know, it is quite uncommon for Phase II trial interim data to be selected for oral presentation. We are hopeful that the promising data from the ongoing trial will demonstrate the potential of the platform in oncology and PDS0101, in particular, in the treatment of advanced HPV-related cancers.
We look forward to sharing the data with the scientific and the investment communities. The most critical limitation to effective cancer immunotherapy has been the ability to induce in the body large numbers of potent tumor-attacking killer T-cells that can infiltrate and kill tumor cells. A recently published preclinical study of the novel triple combination by the National Cancer Institute demonstrated the ability of PDS0101 to promote the induction of large numbers of tumor-infiltrating killer T-cells, when administered in combination with either bintrafusp alfa or M17 -- or M9241 or as a triple combination.
Most importantly, the study revealed that Versamune had effectively recruited a large number of killer T-cells and primed these T-cells to specifically recognize target and kill HPV16 positive cancers, leading to superior regression of advanced tumors with the triple combination. The ongoing National Cancer Institute-led study seeks to study this triple combination in humans. Successful translation of the results from preclinical to human will be significant and could provide a demonstration of the potential of the Versamune-based immunotherapies to overcome one of the major limitations inhibiting broader efficacy of cancer immunotherapy. As I already mentioned, the interim data from this trial will be presented by the National Cancer Institute at the ASCO Conference next month in an oral presentation.
Our second trial is the PDS Biotech-initiated VERSATILE-002 trial. As with the NCI-led trial, we are seeking to confirm the strong synergy between PDS0101 and checkpoint inhibitors demonstrated in preclinical studies. VERSATILE-002 is a multicenter, open-label, single-arm, non-randomized trial of approximately 96 patients, evaluating the combination of PDS0101 with the anti-PD-1 checkpoint inhibitor, pembrolizumab, also known as KEYTRUDA. This combination is being evaluated in first-line treatment of recurrent or metastatic head and neck cancer. Our partner, Merck, is providing the drug and also sits on the joint steering committee for the trial, while PDS Biotech has responsibility for the day-to-day management and financing of the study.
We believe that the combination of PDS0101 and KEYTRUDA, which is FDA-approved as standard-of-care in this indication has the potential to provide significantly improved clinical benefit compared to treatment with KEYTRUDA alone. This means that patients whose cancer has returned or spread following initial treatment will be able to take this chemotherapy sparing combination of 2 immuno-oncology agents, an approach that may be very appealing to patients. Patients are actively being screened and enrolled at multiple sites in the United States, and we anticipate that preliminary data will potentially be available late in the fourth quarter of 2021 or during the first half of 2022.
Similarly to the triple combination trial, a successful trial of KEYTRUDA with PDS0101 that confirms the published preclinical data could justify the evaluation of several of our pipeline products with checkpoint inhibitors.
Moving on to the third trial, the IMMUNOCERV trial. The MD Anderson-led IMMUNOCERV trial is a Phase II trial of PDS0101 in combination with standard of care chemoradiotherapy or CRT for the treatment of locally advanced cervical cancer. The study will investigate the safety and preliminary efficacy outcomes of this combination.
We announced the initiation of the study in October. This study is based on the observation by MD Anderson Cancer Center that cervical cancer patients with tumor infiltrating T-cells may have a better clinical outcomes after CRT treatment. The study is also actively recruiting and enrolling patients, and we anticipate that preliminary data will be available during the fourth quarter of 2021 or during the first quarter of 2022.
Dr. Lauren Wood, our Chief Medical Officer, will provide additional details about our ongoing clinical trials shortly. As I have mentioned before, based on the potential for a unique combination of potency and safety, suggested by our Phase I clinical trial, 2 of our 3 Phase II trials combined PDS0101 with standard-of-care, that has been FDA-approved and shown to be effective in the specific indications.
Now based on the observed efficacy of the PDS0101 monotherapy with respect to CD8 T-cell induction and regression of CIN lesions observed in the Phase I clinical trial, we believe that this ability to combine PDS0101 with FDA-approved standard-of-care mitigate development risk. In addition, if the studies demonstrate significantly enhanced clinical benefits over the standard-of-care alone, without compounding toxicity, we believe that this will present a clear and more rapid path to commercialization of the combination.
After initial commercial approval, our strategy of evaluating PDS0101 in all HPV-associated cancers as well as combining PDS0101 with standard-of-care, we believe also positions us for rapid market penetration and expansion. I'll briefly discuss the target markets for PDS0101. As some of you already may know, the HPV cancer market is large and is expected to remain robust for the next several decades despite the use of preventive HPV vaccines, first introduced in 2006.
There are currently about 43,000 new incidences of these cancers every year in the United States alone. HPV-associated cancer continues to present a critical medical concern, as some of these cancers continue to be on the rise. HPV-associated head and neck cancer, for example, has recently been described as a silent epidemic due to the rapidly increasing incidents of this cancer. Anal cancer incidents has also been steadily increasing. By far, the vast majority of these cancers are caused by HPV16, which is the most oncogenic type of HPV.
Next, I'll provide an overview on the continued development of our oncology pipeline. PDS0102 combines the Versamune platform technology with the proprietary tumor-specific protein or antigen known as T-cell receptor gamma alternate reading frame protein, also known as TARP or T-A-R-P. TARP was identified by the National Cancer Institute and is strongly associated with prostate and breast cancers as well as acute myeloid leukemia or AML. It is estimated that TARP is associated with almost 400,000 cancers each year in the United States, including 90% of prostate cancers, 50% of breast cancers and 100% of AML. AML is a particularly deadly disease with a 5-year survival rate of less than 30%. In a human clinical study in prostate cancer patients, the TARP antigen was found to be highly immunogenic in the patients, leading to a significant reduction in the tumor growth rates.
In preclinical studies conducted at PDS Biotech, PDS0102 demonstrated the ability to dramatically enhance the induction of in vivo TARP-specific CD8 killer T-cells. The majority of the preclinical work for PDS0102 has been completed, and our goal is to move PDS0102 into the clinic next year.
Also in late clinical development is PDS0103. In April of 2020, we announced the expansion of our Cooperative Research and Development Agreement, or CRADA, with the National Cancer Institute to include studies of PDS0103, which combines the Versamune technology with novel peptides derived from the cancer-associated protein known as MUC1. These novel proprietary and highly immunogenic peptides were developed by the Lab of Tumor Immunology and Biology of the National Cancer Institute. MUC1 is expressed in a wide range of solid tumor types, including breast, colorectal, ovarian and lung cancers. In preclinical studies conducted at PDS Biotech, PDS0103 has demonstrated the ability to generate powerful in vivo MUC1-specific CD8 killer T-cells.
In humans, due to Versamune's ability to effectively promote important immunological processes and to activate the type I interferon signaling pathway, we anticipate strong in vivo tumor targeting CD8 T-cells that may present the potential to more effectively treat MUC1 expressing tumors. As part of our collaboration with the National Cancer Institute, the institute is performing preclinical combination studies of the clinical formulation of PDS0103 with other immunotherapeutic agents ahead of the planned human clinical study next year.
Moving on now to our infectious disease pipeline. This March, we announced that the COVID-19 vaccine consortium consisting of PDS Biotech, Farmacore Biotechnology and Blanver received the commitment from the Ministry of Science, Technology and Innovation of Brazil, the MCTI, to fund up to approximately USD 60 million to support the clinical development in commercialization of a Versamune-based COVID-19 vaccine in Brazil. PDS Biotech will be providing Versamune for the program, and our partner, Farmacore is responsible for manufacture of the antigen and also for performing the human clinical trial in Brazil. Farmacore is in active discussions with ANVISA to progress the clinical program in Brazil. Farmacore have indicated to PDS Biotech that they plan to begin the combined Phase I/II trial before the end of the year.
I'll move on now to PDS0202, which combines Versamune with novel influenza vaccine antigens in a preclinical universal flu vaccine. We announced last year that PDS Biotech's collaborator, Professor Jerold Woodward of the University of Kentucky School of Medicine was awarded a grant from the NIAID to support preclinical development of this program. Dr. Woodward initiated those studies earlier this year in partnership with the collaborative influenza vaccine innovation centers network of the NIAID to develop a more durable, broadly protective and longer-lasting vaccine, effective against multiple strains of influenza, specifically including pandemic strains. We anticipate results from those studies and a clinical formulation will be available by the end of the calendar year.
Now I'd like to pass the call to Dr. Lauren Wood, who will provide more comprehensive clinical updates for both our oncology -- for all our oncology programs. Lauren?
Lauren Wood
Thank you, Frank. And once again, thanks to all of you for joining us this morning. As Frank just detailed, we have made significant progress in our oncology pipeline since our fourth quarter call. I'll begin with our ongoing oncology clinical trials. The investigator-initiated study of PDS0101 in combination with bintrafusp alfa, also known as M7824, a first-in-class bifunctional checkpoint inhibitor and M9241, an antibody conjugated cytokine designed to facilitate entry of the cytokine IL-12 into the tumor microenvironment and to enhance the local T-cell response was initiated in June 2020 with encouraging and faster than projected initial approval despite the COVID pandemic. This NCI-led study was a result of independent preclinical animal studies conducted by the NCI, which showed strong synergy between the 3 agents.
Specifically, the triple combination resulted in enhanced antitumor activity when compared to treatment with the individual agents or with dual combinations of these agents. The details and findings of these preclinical studies were published last year in the June 2020 issue of the Journal for ImmunoTherapy of Cancer, also known as JITC. We previously announced that this investigator-led study achieved both its initial safety benchmark, meaning that fewer than 2 dose-limiting toxicities were observed in the first 6 patients who received the triple combination and its initial efficacy benchmark.
The initial observation of objective response in 3 or more of the initial 8 patients indicated that the triple combination was at least 2x more, 100% more effective in reducing tumor burden compared to the standard of care outcomes in this patient population to date. As a reminder, this patient population is very difficult to treat. The best objective responses reported to date in advanced HPV cancer patients who have failed prior therapies is 12% to 24%. Many of these patients have failed multiple treatments before enrolling in the NCI-led trial.
With the achievement of this initial efficacy threshold, the NCI has added a second arm to the trial to explore the effectiveness of the triple combination in patients who have failed checkpoint inhibitors, raising the bar significantly. Advanced HPV cancer patients who have failed checkpoint inhibitor therapy have very few treatment options left. The highest objective response rates reported to date in this population who, in addition, have failed checkpoint inhibitor therapy are generally 10% to 15%.
Dr. Julius Strauss, the principal investigator of this trial will be presenting more mature data from the study at the upcoming 2021 Annual Meeting of the American Society of Clinical Oncology in early June. ASCO is arguably the world's preeminent oncology meeting, and we were thrilled to learn that those data have been accepted for oral presentation as part of the main program. As you know, there are tens of thousands of abstracts submitted to ASCO each year, and only a handful of those are selected for oral presentation. We believe that these data were selected because of the historic difficulty in treating this patient population and the compelling interim data from this trial.
Patients often come to the National Cancer Institute when they have exhausted all other treatment options. Advanced HPV cancer patients enrolled in this study have failed multiple therapies, and we believe that PDS0101's published preclinical efficacy, when combined with these 2 immunomodulating agents demonstrates the potential to significantly improve clinical outcomes for patients with advanced and currently untreatable HPV-associated cancers.
Now on to the PDS-sponsored VERSATILE-002 study. As Frank discussed during his remarks, activation of sites and enrollment in VERSATILE-002 continues to progress, and we currently have 14 sites open to enrollment. As a reminder, The primary endpoint of VERSATILE-002 is the objective response rate or ORR at 9 months following initiation of treatment. There will be a leading cohort of 12 patients to assess safety of the combination and a formal planned interim analysis, evaluating response to treatment in the first 38 patients. We estimate the data on the initial 12 subjects for safety will be available sometime between the fourth quarter of 2021 or the first half of 2022. The study's lead principal investigator is Dr. Jared Weiss, who serves as the Section Chief of Thoracic and Head and Neck Oncology at the University of North Carolina School of Medicine, Lineberger Comprehensive Cancer Center, and we're thrilled to have Dr. Weiss involved in this study.
Moving now to the MD Anderson-led Phase II clinical trial of PDS0101 in combination with standard-of-care chemoradiotherapy for treatment of locally advanced cervical cancer, also known as the IMMUNOCERV study. This study will enroll approximately 35 patients and investigate the safety of the combination and preliminary oncologic outcomes. In addition, it will explore immune priming by PDS0101 as well as other biomarkers of immune response in both blood and tumor tissue. We believe that PDS0101's demonstrated ability to activate the immune system and induce tumor-targeting killer T-cells may provide improved outcomes to patients with cervical cancer. Preliminary data from this trial, we anticipate will be available sometime between Q4 2021 and early 2022. The study is being conducted by Dr. Ann Klopp MD PhD and Associate Professor of Radiation Oncology at the MD Anderson Cancer Center.
Moving now to our infectious disease program and the planned clinical trial of our COVID-19 vaccine, PDS0203. If approved by ANVISA, the randomized, placebo-controlled Phase I/II study will evaluate safety, immunogenicity and preliminary efficacy of PDS0203 in approximately 360 healthy adults. Patients in the study will receive 2 doses of PDS0203, administered 3 weeks apart. Study participants will be divided based on age with an 18 to 55 age group and a greater than 56 years of age group. Low dose and high-dose vaccine or placebo will be tested in each of these age groups. Initial evaluations of efficacy will be conducted starting 14 days following receipt of the second dose of vaccine. Specifically, we're seeking to characterize safety, reactogenicity and validate the induction of SARS-CoV-2-specific neutralizing antibodies as well as CD8 killer and CD4 helper T-cells directed against SARS-CoV-2.
Our co-development partner, Farmacore will be meeting on a regular basis with regulatory officials from ANVISA to review ongoing data from the Phase I/II trial in an effort to react as quickly as possible to results.
Contingent upon release of funds by the Brazilian MCTI, if the Phase I/II study successfully establishes both safety and efficacy, we are prepared to scale up into a Phase III trial to confirm PDS0203's effectiveness in preventing COVID-19 infection. One of the planned analyses in the Phase III design is the assessment of efficacy against variants of the virus. The robust T-cell induction by Versamune may potentially provide protection against currently circulating variance of concerns. PDS0203 is being designed to induce an immune response against conserved regions present in SARS-CoV-2 and to specifically generate long-term T-cell memory, To serve regions of the virus are those that remain stable despite ongoing viral mutations. I would now like to turn the call over to our CFO, Dr. Seth Van Voorhees, to review our first quarter 2021 financials. Seth?
Seth Van Voorhees
Thank you, Lauren, and good morning, everyone. I'd like to turn our discussion to a review of our financial results for the quarter ending March 31, 2021. For the first quarter of fiscal '21, our loss from operations was approximately $3 million versus a loss of approximately $4 million during the same period in 2020, or a net loss of $0.14 per basic and diluted share compared to a net loss of $0.39 per basic and diluted share for the first quarter of 2020.
Research and development expenses totaled approximately $1.4 million in the first quarter of 2021 as compared to $2 million for the first quarter in 2020, a decrease of approximately $0.6 million or 28%. For the first quarter of 2021, general and administrative expenses were approximately $1.6 million compared to approximately $2.1 million for the same period in 2020, a decrease of approximately $0.4 million or 19%. From a cash flow perspective, we started 2021 with approximately $28.8 million of cash and used approximately $3.8 million in our operations in the first quarter of 2021, leaving us with a cash balance at the end of the period of approximately $25 million. Our business strategy allows us to keep our cash burn at relatively low levels as demonstrated by our first quarter results. This strategy utilizes the cash we raised from the capital markets on our oncology development programs, while continuing to develop our infectious disease products through non-dilutive financing sources or out-licensing agreements.
In addition, 2 of the 3 oncology clinical trials, currently underway, are investigator-sponsored studies, which involve low levels of financial commitment from PDS, while at the same time, maintaining 100% ownership of the commercial rights of the Versamune products being investigated. As a consequence, we are able to utilize our cash resources in a most efficient manner to create value for our shareholders.
Thank you for your time today. And I'd like now to turn the call back to Frank for final remarks.
Frank Bedu-Addo
Thank you very much, Seth and Lauren. Before we begin our question-and-answer session, I would like to thank our stellar team members here at PDS Biotech and all of our clinical partners for their untiring work. It is an exciting time at PDS Biotech with the potential of having some solid initial proof-of-concept data for our Versamune platform in oncology next month. It is through their dedication and the expertise of our team that we have been successful in significantly progressing 3 active PDS0101 Phase II clinical trials in oncology, while also continuing to develop our preclinical pipeline. The data now being generated from our ongoing clinical trial programs will serve as the foundation to allow us to build our Versamune-based pipeline into the next generation of cancer immunotherapies as well as novel vaccines that may induce a broader range of protection against infectious diseases.
That concludes our prepared remarks. Operator, please begin our question-and-answer session.
Question-and-Answer Session
Operator
[Operator Instructions]. Our first question today is coming from Joe Pantginis from H.C. Wainwright.
Joseph Pantginis
I have two sets of questions, and I'd like to start with the COVID platform, first. Obviously, you have a very defined program in Brazil and the funding to go along with it. And I guess, I wanted to approach my question this way. How can we view as the importance of T-cells continues to increase in visibility, further potential reach -- I'm sorry, geographical reach of the program. And I'm thinking specifically of all the volatile environments and the significant problems that India is having and discussions about freeing up intellectual property for other vaccines. It's just a very dynamic environment. So I guess I just want to get a sense of potential geographical reach that you might be working on.
Frank Bedu-Addo
Well, Joe, thank you very much for your question. This is Frank. And I think one of the -- I wouldn't call it a challenge, but one of the facts of the matter is that, this program, we anticipate, as it continues to build up, that it will become more and more visible. One of the key things that you did mention that's becoming very prevalent today is the key role or importance of T-cells in robust immunity against COVID-19. One of the things that we have mentioned quite often is the fact that we believe very strongly that the next generation of COVID-19 vaccines should be able to demonstrate robust T-cell responses, importantly, against conserved regions of the virus because we know today that this virus has a very high propensity for mutation, and therefore, being able to generate or develop a vaccine that can provide a broader range of protection becomes very important.
Now we continue to focus on our oncology pipeline. We are providing support to Farmacore in terms of Versamune expertise, but they have the responsibility for developing this vaccine and performing the human clinical trials in Brazil, specifically. So in terms of the regional components, the trial now is really going to be performed in Brazil by Farmacore. However, I think once that data does become available, the initial data does become available, PDS retains the right to be able to develop the vaccine as we see fit, right? So we will continue to evaluate the situation as it progresses. And as data becomes available, hopefully, we will be making the appropriate decisions and determine where to go from there. And one of the things that we've also mentioned right from the start is our goal isn't really to rush to be one of the first to market, right? We've called this a second-generation COVID-19 vaccine. What we would like to do here is to develop a vaccine that has the attributes that are critical for a successful global COVID-19 vaccine.
That means it must achieve or have certain critical characteristics. It should have induced a broad range of immune responses. So not only neutralizing antibodies, but very importantly, CD8 and CD4 T-cells as well as memory T-cells that recognize conserved regions of the virus.
Secondly, it should be stable, should have long-term stability, overcoming the cold chain situation that we see with a number of the vaccines today. And very importantly, it should be safe and very well tolerated. And we believe the diverse immune-based COVID-19 vaccine checks each of these boxes. And so the goal is really to develop this and really make sure that we have something that is highly competitive in the global markets today.
Joseph Pantginis
That's actually really helpful. And thanks for reemphasizing having the second-generation and not necessarily rushing. So thanks for restating that again. My second question has to do with 0101. It's really 2 parts. The first part is a logistical question, saying, obviously, we'd love to know the data, but I can't wait till ASCO. But I guess, can you share with us sort of the general or range of number of patients that we can expect data on and any sort of translational data that might be presented as well, just the types of and scope of data.
Frank Bedu-Addo
Sure. So the abstract will be made available by ASCO on May 19. So you won't have to wait too long to get an insight into what the data looks like. But I think it's going to be in the range of, I would say, probably around 20 to 25 patients. So it will be at least, I would say, approximately midway through the full trial. So I think it will be a robust enough data package that would give us some very good insight into what's actually going on with the triple combination in these patients.
Joseph Pantginis
Got it. Got it. And then the second part is, and this goes to some of your prepared comments and also something that we've discussed before with you. And that is one of the key challenges in IO studies or IO combination studies is how to tease out the impact of a particular asset, in this case, Versamune. So with 0101, as part of your prepared comments, you certainly talked about the preclinical data and study that the NCI have done with regard to the significant increases in the CD8 T-cells. Now I guess, how does -- you guys have given some of your views, and I'd like for you to repeat it, but also how does the NCI view this? Like you said, these are patients that no longer have any options and the NCI's view of the true importance of the significant boost in CD8 T-cells that can infiltrate the tumor and any perceived risks around, again, the concept I started with about teasing out the individual contribution?
Frank Bedu-Addo
Right. No, that's a really good question, very important and something that we have spent a lot of time discussing. And so without really going into the specifics of the data, I think the way the trial was run and the patient population addresses some of these questions. And hopefully, in the next couple of weeks, we will be able to delve much deeper into the data and really answer some of those questions. But we are quite confident that a lot of these questions are addressed in the data package that will be released in the next few weeks.
Lauren Wood
And can I -- Joe. So the other thing that I'd like to add is, is that, your question is very timely. And we believe one of the strengths of the NCI trial is, is that this same group was responsible for conducting the Phase I/II study of bintrafusp alfa M7824 monotherapy in the HPV-advanced cancer population. And there, they saw objective response rate of approximately 30%. Importantly, this same group also conducted the Phase I trial of the immune targeting cytokine M9241, NHS IL-12. There, they saw 0 objective response rates in that human clinical trial. Although, they do see 5 or 6 patients that had stable disease. So I think the NCI Group is uniquely positioned to be able to evaluate the activity and the efficacy preliminarily of this triple combination because they did the monotherapy studies of the individual investigational immunotherapeutic agents, apart from PDS0101. And so again, as we highlighted earlier during our comments, it was quite impressive in terms of the preclinical data.
Clearly, dual combination therapy was superior to monotherapy in the preclinical studies and clearly triple combination therapy was superior to the dual combination therapy. So in the context of that preclinical translational background, we anticipate that we will see more potent outcomes with the triple combination in humans and then have to evaluate those outcomes in the context of what's already been documented with treatment with the monotherapy agents. And the NCI Group is well-poised to be able to comment on that.
Joseph Pantginis
Got it. And what I think is a real important benchmarking and looking forward to the data.
Operator
[Operator Instructions]. Our next question is coming from Leland Gershell from Oppenheimer.
Leland Gershell
Congrats on all the great progress. I wanted to ask on the VERSATILE study, once we begin to see data from that and as you contemplate further development, sort of a regulatory question, how you would see a registration study design? I mean, would that be kind of KEYTRUDA plus/minus 0101? Would we need to have survival data for approval? Could you file off of response rate? Maybe just give us some color on your thoughts there for what that would look like? And then also a question on the COVID-19 side, just kind of maybe teeing off of dose question, just more in a focused way? Are there any gating factors that we're waiting for from ANVISA? Or is it just a process as a review and kind of complete their assessment for the trial to begin?
Frank Bedu-Addo
Lauren, do you want to take the VERSATILE question? And then after you're done, I'll address the COVID question.
Lauren Wood
Great. Yes. So thanks for your question. We do anticipate that the FDA would want to see a randomized Phase II trial that was blinded for a registrational trial. They made it pretty clear in the statement of July of 2018 that they really want to see randomized trials that definitively established activity of the agents. And so as you mentioned, it would likely be KEYTRUDA with and without PDS0101 in a randomized trial. We clearly would be going for primary endpoints of objective response rate, first and foremost.
Our target objective response rate for the VERSATILE-002 study is 33%. So as people may be aware, with pembrolizumab monotherapy in the KEYNOTE-048 study, the objective response rate is approximately 20% and those who have adequate tumor marker expression of PD-L1. 20% is 1 in 5 patients. And the goal of the VERSATILE-002 study is to see objective response rates of 33% or more, which moves the needle from 1 in 5 patients responding to 1 in 3 patients responding. So objective response rates would be the primary outcome, probably also accompanied by duration of response as a key secondary endpoint and then subsequently overall survival. We believe those would be the 3 major endpoints in a randomized trial that the FDA would be considering. Of course, the design of any trial is going to be driven by the objective data that's observed in our VERSATILE-002 study. And so there may be flexibilities for adaptive trial designs, depending upon what the data should -- yes, would be the most efficient regulatory pathway to proceed with. But we believe...
Frank Bedu-Addo
So Leland, does that address your question before I move on to COVID?
Leland Gershell
That's helpful, Frank. Please go ahead.
Frank Bedu-Addo
Okay, thanks. So regarding any gating items that are necessary to get the trial going. So as I mentioned in my remarks that Farmacore is responsible for the manufacturing of the antigen that's going to be used in the trial. PDS will be providing Versamune. The Versamune is ready to go. And Farmacore is in discussions with ANVISA, which is their regulatory agency, regarding providing a final package prior to entering into human clinical trials.
Completion of their manufacturing process is going to be important in the final documents that are provided to ANVISA. So as we -- as far as we understand it today, that would be a key gating item in their discussions with ANVISA, given them the green light to initiate human clinical trials, getting the manufacturing done and providing what we would call in the -- with the FDA, our CMC package or the IMPD package to allow them to initiate those clinical trials.
Leland Gershell
Got you. Okay. That's helpful. And then one last question, if I may. I mean given the potential for the Versamune platform and a lot more that could be done versus your bandwidth. Just kind of curious if you may see kind of partnerships or sort of deals with third-party companies materialize down the road, as others become more and more aware of the potential of the platform and what they may be able to bring to bear with regard to incorporating that with their own strategies as obviously, you move forward with your core programs.
Frank Bedu-Addo
Yes. No, that's very important. So as you may notice, our primary focus is immuno-oncology, right? And that's really one reason why our infectious -- the 2 infectious disease programs actually being run pretty much 100% by the partners. We will probably never have the resources we need to really develop all the products we could potentially develop with Versamune in immuno-oncology. Now our current Phase II clinical trials provide a very important proof of concept in immuno-oncology. And we believe that this is going to be very critical for our rapid expansion and growth in terms of developing these immuno-oncology products. This proof of concept, the first real proof-of-concept data is what's going to be presented at ASCO next month. And so we anticipate that, that would provide a springboard to really start the second portion of our business plan, which is to partner with other companies developing immunotherapy.
So other companies will have suitable antigens that we could combine with Versamune to develop some of these more reflective T-cell activating immunotherapies. But what you said is absolutely correct. The proof-of-concept data that we are currently generating with these multiple Phase II clinical trials is really what the industry needs to see to confirm or validate the potency and the potential of this technology to be utilized in multiple immunotherapies and also, very importantly, in partnerships with other companies to build out these programs.
Operator
We reached the end of our question-and-answer session. I'd like to turn the floor back over to management for any further or closing comments.
Frank Bedu-Addo
Thank you very much, and thank you very much to all for your continued interest in PDS Biotech. We believe that 2021 will continue to be an exciting year for the company. We have multiple ongoing clinical trials of PDS0101 in various advanced HPV-associated cancers. And as I mentioned, interim data from our most advanced proof-of-concept Phase II trial will be presented on June 7 at the ASCO Conference in an oral presentation. The presentation abstract will be made publicly available by ASCO on May 19. We anticipate that interim data will provide validation of Versamune and PDS0101's potential to overcome the critical limitation of immunotherapy by activating large numbers of potent tumor-targeting killer T-cells in vivo and therefore, facilitating more effective therapy. We anticipate that this will also provide a springboard to focus primarily on building out our oncology pipeline and also to partner with other companies to accomplish this goal.
We appreciate your ongoing support in this pursuit. For more information about the company and our ongoing clinical trial, please visit our website at pdsbiotech.com. Thank you very much again.
Operator
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time. And have a wonderful day. We thank you for your participation today.
Just listened to new PDSB interview with Frank, Lauren and Seth, well worth listening to entire 42 minute interview. Please let me know if I missed anything or got something wrong. I am as optimistic as ever about the possibilities for PDS investors.
Interview Link
Here are some of my notes with regards to the interview. If you don't have time to listen to entire interview, I recommend jumping to minute 36 and listening to the end where you will hear them discussing the following:
At about the 36 minute mark, Frank said “Having an oral presentation at ASCO on interim data is not at all common and they are quite enthusiastic about that.”
He went on to say “The next 2 trials combine Versamune with current standard of care and since they are combining with current standard of care, if they are able to demonstrate increased efficacy without increased toxicity, they have a rapid and clear path to commercialization.”
At 38 minute mark: Seth said "The 3 current clinical trials are with a single antigen, HPV16. They have identified 74 antigens where their technology is compatible with the Versamune platform with 3 antigens currently under preclinical development. If they are able to demonstrate efficacy in any of the 3 current clinical trials, it will open up a wealth of opportunities for both in house development as well as out licensing opportunities.
Frank said "Clinical trials are real Proof of Concept trials for Versamune technology platform. Once they demonstrate technology works, it opens up significant range of opportunities."
Preclinical development discussed during last minute:
PDS0102 in prostate, breast and AML
PDS0103 breast, lung partnered with NCI and studies to start soon.
Hope to get 1 or 2 of them into clinical trials next year.
Here are notes from earlier in the presentation:
PDS 0101 target 10 different types of cancer
Not all T cells are created equal. Versamune induces the right type, in right quantity and potency to address the correct targets.
Types of tumors targeted, 0101 addresses HPV16 cancers, 3 trials.
NCI trial 0101 combined w 2 other therapies.
Studied in HPV associated cancers, broad range of cancers being targeted.
Checkpoint naïve as well as Checkpoint refractory who have advanced disease w at least 1 or more previous therapies. In preclinical models, examined alone, in 2 combos and in triple combo. Triple combo led to HPV specific T cells migrating to the tumor. At least 3 or more out of 8 responses led to trial advancing. Data to be presented at ASCO.
Additional data to be presented include 12 patients enrolled in study in Q4 plus additional data in 1Q 22
MD Anderson trial late Q4/1st qtr 22
Long article but worth the read, even if from Seeking Alpha. I recommend everyone read this and share with others. Touches on so many valid points.
Link to article
Operation Warped Screed: The Government Threatens To Suspend The COVID Vaccine Intellectual Property
Apr. 26, 2021 4:30 PM ETAZN, BNTX, FUJIF...41 Comments19 Likes
Summary
The Biden administration is being pressured to suspend the intellectual property of companies that have developed the COVID-19 vaccine and antibody therapies.
The intellectual property possessed by companies that helped them develop a COVID-19 vaccine as well as antibody therapies offer means to develop vaccines and therapies to address future virus variants.
Suspending the IP will not lead to more vaccinations across the globe with better results. Instead, they will likely create a different set of complex problems.
Background
Pfizer (PFE)/BioNTech (BNTX)and Moderna (MRNA) using mRNA technology and Johnson & Johnson (JNJ) using adenoviral vectors developed different COVID-19 vaccines. The vaccines are not copycat formulas designed to artificially extend company patents or hamstring generics producers. They are not priced extortionately. Rather than being just as good therapies or drugs already on the market, the simple fact is they are novel, they work and are the result of proprietary intellectual property.
Having developed COVID-19 vaccines, it is true the companies stand to earn billions of dollars in profits. Even though J&J has indicated they will sell the vaccines as a non-profit, that is likely to remain true only through the initial phase, as it is improbable that any of the vaccines will provide 100% cures or eradicate the virus causing the disease. Consequently, additional shots will be needed and there will be more profits in later years for these and other pharma/biotech firms. However, the vaccines are like any other novel drug, their commercial value is based on their uniqueness and is their competitive advantage.
So, what happens if you give away the intellectual property? By its very definition, it is no longer a competitive advantage and it no longer has unique value; which means it affects future vaccine pricing and profitability. When the IP that is the basis for the drug is no longer unique but capable of imitation, the drug becomes a matter of competition on price. This is apparent when formerly novel drugs lose patent protection and the barriers to entry are lifted, we know generics then enter the market to compete on price and, as experience shows, will take market share away from the once novel drugs.
This means any discussion of who possesses the intellectual property is neither academic nor theoretical. It is a real-world matter that is a foreboding threat to the companies that worked to develop a COVID-19 vaccine in an astonishingly short period of time. Considering the previously fastest vaccine developed was for the mumps and that took four years, that a coronavirus vaccine was developed in under a year is exponentially quick.
In truth, under normal circumstances making a vaccine can take up to 10–15 years. This is because of the complexity of vaccine development and the incumbent costs, which are usually between $31M and $68M. What reduced the time to develop the COVID vaccines was that, with Operation Warp Speed, the government partnered with companies and multiple institutions, including the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), to develop, manufacture, and distribute 300 million doses even before any company could know their vaccine was going to work.
To be certain, it was said by many scientists that it could not be done in so short a period of time. Early on Dr. Anthony Fauci and others gave a best-case timeline of 18 months. Yet it was sooner and, beyond the funding, the truncated timeframe was the result of existing intellectual property that had been in trials on many kinds of coronaviruses – including four that can cause the common cold, as well as the coronaviruses that sparked the SARS, or severe acute respiratory syndrome, epidemic in 2002 and the emergence of MERS, or Middle East respiratory syndrome, in 2012.
Still, without the federal financial backing, such an expeditious development would not have been possible, as it was highly unlikely that the various companies would have been able to commit to a singularly costly and maniacal focus.
Companies Committed to Developing Covid Vaccines or Antibody Treatments
Though not an exhaustive list of drug makers who are under contract with the U.S. government to provide either a COVID-19 vaccine or antibody drug shows the extent of the U.S. effort to generate vaccines or antibodies for the American public. Those listed are in alphabetical order:
AstraZeneca (AZN)– In May, AstraZeneca signed a contract for $1.2 billion to boost access to its COVID-19 vaccine. In October, the drug maker signed a second contract for $486 million for the U.S. to secure 100,000 doses of its experimental COVID-19 antibody drug and support clinical trials for the drug.
Cytiva, a division of Danaher (DHR) – In October signed a contract for $31 million to scale up production of materials needed to produce COVID-19 vaccines, such as liquid and dry powder cell culture media, cell culture buffers, bioreactors, and mixer bags.
Eli Lilly (LLY) – In October, Eli Lilly signed a $375 million contract to supply 300,000 vials of its COVID-19 antibody drug, which was granted emergency authorization by the FDA in November. In early December, the drug maker signed another $812.5 million contract to supply 650,00 more doses of the drug.
Emergent BioSolutions (EBS)– In June, Emergent BioSolutions signed a $628 million contract to ramp up its contract development and manufacturing capabilities to expedite the delivery of COVID-19 vaccines.
Fujifilm (OTCPK:FUJIF) – In July, Fujifilm signed a $265 million contract to manufacture COVID-19 vaccines.
Johnson & Johnson – In August, Johnson & Johnson signed a more than $1 billion contract to supply the U.S. with 100 million doses of its COVID-19 vaccine if it is authorized.
Moderna – In August, Moderna signed a $1.5 billion contract to supply the U.S. with 100 million doses of its COVID-19 vaccine, if it is authorized.
Novavax (NVAX)– In July, Novavax signed a $1.6 billion contract to supply the U.S. with 100 million doses of its COVID-19 vaccine, if it is authorized.
Pfizer & BioNTech – In July, Pfizer and BioNTech partnered to sign a $1.95 billion contract to supply up to 600 million doses of its COVID-19 vaccine. Under the contract, the U.S. would receive 100 million doses of the vaccine with the opportunity to secure 500 million more doses, but the U.S. did not secure the additional doses.
Regeneron (NASDAQ:REGN) – In July, Regeneron signed a $450 million contract to manufacture thousands of doses of its COVID-19 antibody cocktail, which was granted emergency authorization in November.
Sanofi (SNY) & GlaxoSmithKline (GSK)– In July, Sanofi and GlaxoSmithKline partnered to sign a $2.1 billion contract for development of the drug maker's COVID-19 vaccine as well as an initial supply of 100 million doses.
Bigger Than Expected Covid Market, Large Orders, And Good Production Make Novavax A Buy
Moderna's Value Beyond The Vaccination Bonanza
Moderna: Only One Question Matters Thursday
Analysts from Bernstein estimate the market for COVID-19 vaccines at $39 billion in 2021, falling over 40% to $23 billion in 2022, and falling another 40% to $13 billion in 2023. However, this does not account for the expected need for booster shots each year to attend to variants or continue the immunity, which is not lifetime as with some other vaccines.
That Moderna, Pfizer, J&J, and AstraZeneca are planning to adapt to meet the challenges of COVID-19 is only possible because they have the intellectual property that allows them to conduct research to further vaccine development in a shorter timeframe.
This, of course, raises a couple of points.
The belief is the coronavirus is expected to continue to evolve and create new variants. Pfizer CEO Albert Bourla said people will “likely” need a third dose of a Covid-19 vaccine within 12 months of getting fully vaccinated. He also said it’s possible people will need to get vaccinated against the coronavirus annually.
Both Pfizer and Moderna see additional vaccinations as likely to be needed. Even after the pandemic is contained, the coronavirus could circulate "in pockets" around the globe, potentially leading to new outbreaks, said Moderna chief commercial officer Corinne Le Goff in a presentation Wednesday.
Moderna CEO Stephane Bancel told CNBC's Squawk Box that the Massachusetts-based biotechnology company is developing a vaccine that will protect against both COVID-19 and the flu, reducing the number of booster shots recipients will have to get.
"This virus, as I've said before... is not going to go away. It is not leaving the planet. We have to live with it, and we're living with it like we live with flu... And so, what we're trying to do at Moderna, actually, is to get a flu vaccine in the clinic this year and then combine our flu vaccines with COVID vaccines so that you only have to get one boost.”
Obviously, unlike the polio vaccine with its lifetime immunity and, more like the flu vaccine with its annual vaccination, COVID-19 will require what appears to be an annual vaccination, one that would require an annual developmental adaptation to meet the changes wrought by virus variants. Such a vaccine is made possible by applying and extending the intellectual property the companies possess.
But wait, rather than suggesting the answer to the business question lies in science, we have politics seemingly hijacking the discussion, with the potential of upending the equation and, without being melodramatic, will likely lead to unseen numbers of deaths.
Politics Not Science
Some holders of high office were skeptical of the early efforts to develop COVID-19 vaccines in record time, indicating they would not trust any vaccines developed in such a short period of time – translated, that means any vaccines developed under the watch of the former occupant of the Oval Office. Yet here we are, with an ever-increasing percentage of the U.S. population having received a shot with one of the three vaccines approved in the U.S. for emergency use.
Moreover, we see the discussion of the U.S. reaching that nebulous state of herd immunity and businesses beginning to see the proverbial light at the end of the tunnel, as they can once again open for business. Workers, at least those who believe they will make more money working than being on unemployment, will get back to not merely providing for themselves and their families but furthering their career aspirations. One might even say it is the “dawning of a new day in America.”
But this being today’s America, it appears the current political establishment is proposing changing the calculus. Why you ask? Perhaps a little context is needed.
We Are Not Safe Until Everyone Is Safe!
Hyperbolic statements by politicians are expected and, relatedly, some U.S. congressional politicians seek to influence and engage action by the Biden administration by arguing the U.S. and other wealthy countries are controlling most of the supply of COVID-19 vaccines, as inoculation efforts in other countries progress at a slow pace.
That the vaccines were developed by smart people who work for smart companies in the U.S. seems to also be lost on the well-meaning. Not to be too snarky, but U.S. companies developed the vaccines from their intellectual property and the government is paying for the shots to enable its citizens to get first crack at having our population vaccinated. Logical action by a country that seems roughly the equivalent of putting your life vest on first before helping anyone else.
In fact, the Trump administration spent U.S. tax dollars wisely to engage pharma and biotech in what was hoped to be a truncated development process (moving from years to months). Clearly, this investment worked. Based on Operation Warp Speed, we have vaccines that were developed for a novel infection in record time. This reflects well on American ingenuity and for making the point that a capitalistic society has its benefits. Still, there are those politicians who appear to believe that is a privilege too far and we should share with the underdeveloped nations – aka, poorer countries - even if to the detriment of those “greedy” drug companies!
Of course, their idea of sharing is not selling drugs at cost or even charitably giving them to the underdeveloped nations. No, not good enough. We should simply give those who ask the intellectual property to make their own, or at least try, and these politicians want to use the governmental power to make it happen… and they can.
March-In: The Government's Rights
The drug makers argue that stripping them of their patent protections could backfire at a time when they are working to produce boosters to combat virus variants. And they say there are better ways to ensure the vaccines reach the world's population.
The debate will come to a head over the next few weeks as the Biden administration makes critical decisions about who owns the knowledge associated with COVID-19 drug inventions that could impact vaccine pricing and production for years to come.
Currently, vaccines are free to all Americans during the emergency pandemic period, and Biden says the country will have more than enough supply to vaccinate everyone currently eligible. But vaccines may not be free in the future should Americans need boosters and, perhaps, therein lies the rub.
This means Biden will soon have to decide what to do about a rule proposed by the National Institute of Standards and Technology in the final weeks of Donald Trump's presidency, which could help drug companies maintain complete control over drug prices, even when taxpayer dollars have funded much of the research and development. As such, Biden has the ability to choose a different course under a previous act and, as his actions have shown, whatever Trump was for, Biden is against. (Disclosure: I voted for neither.)
Specifically, the 1980 Bayh-Dole Act allows for the government to "march in" and issue a compulsory license for a federally funded invention if the invention is not available to the public under reasonable terms. Practically, this means the federal government could break patents for federally funded vaccines or drugs to authorize generic competition if regulators determine the price is exorbitantly high. Trump's proposed rule would modify the Bayh-Dole Act in ways that weaken the ability by saying the government cannot use its march-in authority solely based on price. Comments on the proposed rule closed April 5.
But stand by, Health and Human Services Secretary, Xavier Becerra is an advocate of march-in rights. Before joining the Biden administration, he led a coalition of states asking the Trump administration to use march-in rights to lower the cost of the COVID-19 drug remdesivir or allow states to take action.
Joe Allen, executive director of the Bayh-Dole Coalition, whose members include drug makers, says the lawmakers misapprehend the act and their efforts could backfire. Allen argues that Congress never intended the government to set prices on products and the law makes no reference to a reasonable price dictated by the government. He says advocates and democrats have been purposefully misinterpreting the law for years.
"It will stop collaboration," Allen said, of enforcing march-in rights. "The danger is the next time you have a pandemic, are companies going to jump in to partner with you (the government)?"
COVID-19 drug and vaccine contracts vary on march-in rights. Moderna's contract contains the standard march-in clause, and Novavax's vaccine contract generally tracks with the Bayh-Dole Act, according to Knowledge Ecology International, a nonprofit group whose precursor organization was founded by consumer advocate Ralph Nader. Johnson & Johnson's contract limits march-in rights to the time during the current pandemic. Pfizer's vaccine was developed entirely with private funds and prohibits the government from marching in, so suspending their IP might be an illegal move.
Nonetheless, advocates and developing nations are lobbying the World Trade Organization, which arbitrates international patent disputes, to suspend some intellectual property rights for COVID-19 vaccines and treatments. Further, some U.S. House Democrats are increasingly urging Biden to have the United States join the effort. Many wealthy countries have begun their vaccine rollout, but less developed nations have not and it could take three to four years for them to fully vaccinate their citizens.
India and South Africa are leading a multi-country push to get the WTO to waive drug makers' exclusive rights to manufacture COVID-19 vaccines and therapies to increase supply quickly. The United States, the European Union, and the United Kingdom do not support this initiative, but advocates want the Biden administration to reconsider it.
However, drug makers and businesses remain firm in the belief that waiving intellectual property protections would not speed up production and would cause more harm than good.
"Eliminating those protections would undermine the global response to the pandemic, including ongoing efforts to tackle new variants. They would also create confusion that could potentially undermine public confidence in vaccine safety, and create a barrier to information sharing," the Pharmaceutical Research and Manufacturers of America, the drug industry trade group, wrote in a letter to Biden asking him not to support the waiver.
A coalition of business groups, including the trade groups for biotechnology firms and medical device makers also sent a letter to the Biden administration asking it to help increase vaccine production through partnerships between private companies, and not by breaking patents. Scaling up vaccine production is complex, and they argue that creating partnerships between drug makers is much more efficient than releasing a vaccine's recipe to the public.
Robert Grant, an international affairs specialist with the U.S. Chamber of Commerce, a business group that counts drug makers among its members, said that intellectual property has not been a barrier to distributing vaccines in the past. He urged the Biden administration to focus on licensing and partnerships, rather than waiving patents. It's much easier for a government to work cooperatively with an industry partner rather than issue a compulsory license to force a drug maker to allow other firms to manufacture its product.
The Status of Global Vaccinations
Wealthy nations such as Canada, the U.S., and Japan have secured ample vaccines for all willing residents within this calendar year and have generally supported global policies that allow drug companies to negotiate and voluntarily set the price and production level of coronavirus vaccines. The U.S., the U.K., and Switzerland, echoing the concerns of drug makers, reportedly opposed efforts early in the pandemic to share intellectual property and technology for coronavirus vaccines and treatments despite global need.
According to one complaint, wealthy countries representing just 16 percent of the world’s population have already secured more than half of all Covid-19 vaccine contracts. And current projections show that much of the middle-income nations and developing world will not achieve widespread vaccinations for years. Some projections predict that low-income countries such as Mali, South Sudan, and Zimbabwe may not achieve significant levels of vaccination until early 2024.
Does this justify the suspension of vaccine IP? If you think so, you have not been paying attention.
Instead of giving up the IP, why not return to the point where the U.S. has backed the so-called COVAX Facility, an underfunded, multinational public-private partnership designed to distribute vaccines to middle- and low-income countries through donations and private purchases of vaccines. Under the COVAX plan, which the U.S. is supporting with $4 billion in funds, pharmaceutical companies can either directly distribute their vaccines or license partners to manufacture vaccines abroad. This is something these mature and sophisticated companies have the capabilities to accomplish.
For example, the Serum Institute of India has partnered with AstraZeneca to manufacture more than 300 million doses through COVAX for over 100 low-income countries by June. But that total represents about 3 percent of the population of the countries slated to receive the vaccines.
The European Union (EU) sealed a deal with Pfizer/BioNTech for the supply of up to 1.8 billion doses of their COVID-19 vaccine - Reuters. This marks the third contract with the two companies, which have already agreed to deliver 600 million doses under two previous contracts. Earlier this month, the EU exercised its option to purchase extra 100 million doses, bringing the total number of doses to be delivered to 600 million under deal signed on Feb. 17, 2021. Also, the EU is likely to receive a total of 250 million doses in Q2 2021 after Pfizer raised its second-quarter deliveries by 25% on April 14.
Johnson & Johnson's single-shot COVID-19 vaccine is expected to be imported to India by June-July 2021 - report. The vaccine will be imported for "fill and finish" which is the final step in the manufacturing process. J&J is working closely with Indian pharma company, Biological E to facilitate the ongoing tech transfer to India.
In February, Biological E told Reuters that it is looking to contract-manufacture roughly 600 million doses of JNJ's COVID-19 vaccine annually. Biological E’s very own vaccine candidate developed with Baylor College of Medicine in Houston and U.S.-based Dynavax Technologies is undergoing clinical trials in India, with late-stage testing due to begin in April. India has said it would fast-track emergency approvals for COVID-19 vaccines authorized by Western countries and Japan, paving way for the possible imports of Pfizer and Moderna shots.
While this leaves many underdeveloped nations wanting, it is a fact that as the COVAX Facility initiative to ensure equitable access to COVID-19 vaccines begins to roll out doses in Africa it's unclear what will happen in countries that long denied COVID-19’s very existence – or claim to have already solved the problem.
In countries where no significant proportion of the population is vaccinated, there is a huge risk of sustained community spread of COVID-19 over a prolonged period. The longer the period of sustained community spread, the more likely that the virus will mutate. And this means it could be a breeding ground for the new coronavirus – SARS-CoV-2 – to mutate into more aggressive variants. The mutated variants from the unvaccinated population will be able to infect even those in the vaccinated population.
However, it is worthwhile pointing out that many of these underdeveloped nations are among the most corrupt countries in existence. Which raises the question of fraudulent drugs. Not a novel thought.
Covid & Corruption
Pfizer has identified in Mexico and Poland the first confirmed instances of counterfeit versions of the Covid-19 vaccine it developed with BioNTech, the latest attempt by criminals trying to exploit the worldwide vaccination campaign.
The findings are the most recent involving an effort between law enforcement and drug makers such as Pfizer, Moderna, and Johnson & Johnson to stem criminal activity related to the Covid-19 vaccines. According to Interpol – an international police organization – criminal gangs will likely attempt to get their hands on the new Covid-19 vaccines, potentially disrupting supplies of the crucial shots as they become available. The global rollout of shots has provided criminals a fresh opportunity to take advantage of unsuspecting people.
This problem would be compounded by allowing the IP for the vaccines to be given out to nations that, while underdeveloped economically, have clear problems with corruption and, with it, the potential for further criminality. The economically fragile countries that might have a high need for vaccinations are also among the most corrupt.
Sorry if I appear skeptical of giving the vaccine IP to such countries or the state-owned drug manufacturing companies within them. In truth, it is likely that any vaccines even charitably given to these countries would end up, like UN economic relief, in the hands of corrupt officials and their representatives and not in the arms of the citizens in need of vaccination against COVID-19. That the story is sad does not make the outcome of getting people vaccinated any more likely.
Further, there should be no doubt that China will use access to the technology transfer to further their global ambitions. It would be political and strategic naiveté to not expect China to seek vaccine dominance. Rather than handing the IP to an adversary, this unpalatable potential demands the need to continue with the effort to engage alliances.
The truth is the demand for knockoff vaccines will be filled by Indian and Chinese companies that don’t do business with Western drug makers and are eager to exploit America’s advanced technology without paying for it. They will also be unbound by American safety standards. But, perhaps, John Kerry can use this as a negotiation tool in achieving greater cooperation in the effort to stem climate change. (Clearly a snarky comment, but is it wrong to suggest?)
Even With A Recipe There Are Problems
Let’s begin with the obvious… even the most capable of companies will have problems. For example, human errors at a manufacturing plant forced Johnson & Johnson to throw out 15 million doses of its COVID-19 vaccine – enough to vaccinate 7% of the U.S. adult population.
But, while errors with an impact of that magnitude sound shocking, they are also a reminder that the U.S. vaccine manufacturing process has strict quality control measures designed to catch these problems before they reach the public.
Vaccine manufacturing is complex, with many potential points for errors. The multiple layers of quality checks by the producer and external inspectors throughout the process are essential to protect public health.
After authorizing a vaccine, the U.S. Food and Drug Administration must approve and regularly inspect each vaccine manufacturing facility. Before each batch of vaccines is released by the FDA, it undergoes rigorous and extensive testing to ensure vaccine safety. In the case of COVID-19 vaccines, manufacturers are required to submit the results of each quality control test for each batch of vaccines 48 hours prior to its distribution. This stringent quality control process has led to what the FDA describes as the safest vaccine supply in U.S. history.
The quality control process is also how Johnson & Johnson discovered defects within the batch of 15 million doses at the Emergent BioSolutions facility. The U.S. government’s Operation Warp Speed has also been involved in quality control. At one point, it deployed 16 Department of Defense personnel in two manufacturing sites to fill gaps in the quality control workforce so production could continue.
While these issues show that the U.S. drug industry has work to do to minimize manufacturing errors, can the world be expected to develop similarly safe and efficacious drugs when they do not have such meticulous attentiveness and oversight?
Given the problems with the quality of drug development in countries like China and India – countries with vast experience in drug development – to give intellectual property to other countries and expect quality products that are fully efficacious is disconnected from reality, one where false labeling and impurities are common and can cause unwanted pharmacological and toxicological effects. Impurities can produce organ damage-causing renal and liver failure. False labeling can lead to precipitated disease progression, which in turn results in negative physiologic effects and treatment failure.
No one would argue the degree of truth in the somewhat hyperbolic and overgeneralized statement that “We’re not safe until the world is safe.” However, that does not mean “vaccines recipes for everyone” is the only route. Such thinking fails the question of what can be learned from reading “The Passage” trilogy by Justin Cronin. There are ways to protect a country, even if some think them ethnocentric.
Still, it is one thing to share our vaccines with poorer nations and entirely another to willingly give up the intellectual property developed by the vaccine makers that can serve us well going forward.
In fact, one might argue this fails the test of gravitas, as it consigns to the decision-making process a “one best way” to help the underprivileged poor.
Sorry, while I may give money to homeless people hanging out on the corner, I am not inviting them to live with me. While I accept the judgment that comes from that statement, it is analogical. Businesses can share with others without giving up their recipes. KFC might hand out food to the homeless, but it is illogical to suggest they provide homeless shelters in their restaurant locations and give anyone who asks their secret recipe of eleven herbs and spices.
Okay, maybe we do have politicians who believe that is a great idea. But, those folks have their minds already made up. There is little that is likely to dissuade them of their belief that suspending IP is the path to global vaccinations. But, I am concerned about decisions by the “big guy” - the current occupant of the Oval Office - who is clearly listening to fellow politicians who strongly consider lifting intellectual property protections afforded to manufacturers of the COVID-19 vaccines.
While such a move would allow other countries to attempt (emphasis on the word – attempt) to replicate existing vaccines, problematically it would allow companies and countries that do not adhere to the same quality standards and who are likely to be willing to trim costs of production that could lead to inferior or even contaminated vaccines that would underperform and fail to prevent people from being infected by the virus or, worse, injure or kill people because of the contamination of the poorly manufactured vaccines. What then do we say to engage the less informed, less educated people in these underdeveloped nations, about the importance of being vaccinated?
Developing Novel Drugs Is Neither Cheap Nor Easy
It is well understood that much of the world still does not have access to vaccines and, as a result, it could be 2023 or 2024 before the entire world gets completely vaccinated. As such and unexpectedly, the corollary argument is that monopolistic control over life-saving medicines is akin to “vaccine apartheid” or “vaccine inequality” and is not “social justice.”
However, the reality is the financial commitment made by drug developers is not always realized with a drug that is approved and commercialized. In fact, we know that the time from drug discovery through development takes about 12 years and only 5 in 5,000 drugs that enter preclinical testing progress to human testing, with just one of the five drugs tested in people is approved. The chance for a new drug to actually make it to market is, thus, 1 in 5,000. Not very good odds, even when money is not the issue.
Moreover, developing a new prescription medicine that gains marketing approval is estimated to cost drug makers $2.6 billion, according to a 2019 study by Tufts Center for the Study of Drug Development and published in the Journal of Health Economics. This is up from $802 million in 2003 – equal to approximately $1 billion in 2013 dollars, and thus a 145 percent increase in the ten-year study gap. Furthermore, while the average time it takes to bring a drug through clinical trials has decreased, the rate of success has gone down by almost half, to just 12 percent.
Tufts breaks down its $2.5 billion figure per approved compound to include approximate average out-of-pocket cost of $1.4 billion and the expected returns that investors forego while a drug is in development of $1.2 billion.
Furthermore, the estimated cost of post-approval research and development of $312 million “boosts the full product lifecycle cost per approved drug” to close to $3 billion. Also, additional R&D costs that would be applicable to COVID vaccines include studies to test new indications, new formulations, new dosage strength and regimens, and the need to monitor safety and long-term side effects in patients, as required by the FDA as a condition of approval.
As previously stated, the IP developed by pharma for COVID vaccines are not copycat formulas but truly novel drugs developed by novel intellectual property owned by the companies. Consequently, it is without question that intellectual property has been at the forefront of drug business development and, in greater measure, is the coin of the realm for pharmaceutical and biotech companies seeking to further R&D and develop their product portfolios that aid mankind. Not only is it the basis for scientific breakthroughs, it is the basis for business success.
After all, those companies that have developed or are developing vaccines or anti-body therapies for COVID-19 are businesses for profit. It is the successful development of drugs that meet patient needs and are commercialized – for profit – that enable the drug companies to reinvest in R&D to create newer drugs to meet the ever-expanding challenges of a population with increasing co-morbidities. That this seems to be lost on politicians would – in support of Hanlon’s Razor – assume stupidity or malice aforethought. With politicians, it is often hard to discern which might offer the best explanation. Nonetheless, the temporary suspension of intellectual property protections that the Biden administration is contemplating would apply to all medical technologies to treat or prevent Covid-19.
Relatedly, the White House convened a meeting of deputy-level policymakers on March 22, a senior administration official said, but they reached no final decision. Hopefully, it was because someone recognized the folly of the proposal. But I am not holding my breath.
There is also the real risk of having to develop new vaccines altogether to combat the new virus strains, which can be deadlier than the circulating ones. Thomas B. Cueni, director general of the International Federation of Pharmaceutical Manufacturers and Associations, argued that waiving intellectual property rights is not the way to get everyone vaccinated. Cueni suggested that abrogating a patent would discourage companies that have been working incessantly on developing these vaccines within tough time constraints. It would also indicate the companies do not and would not have intellectual property rights even during a global catastrophe such as this or future pandemics; something that would reduce their incentive to rapidly develop vaccines in future emergencies.
"Taking away patents now or imposing a waiver wouldn't give you a single dose more," said Cueni. Instead, he argues that the issue is not about the possession of intellectual property but about managing the complex logistics of rolling out vaccines from credible drug developers.
Relatedly, the manufacturing capacity for vaccines is well below the levels necessary in an epidemic or pandemic. This is because it is often expensive to maintain those plants between health crises. After the emergence of COVID-19, it took months to build up the ability to produce more vaccines, in part because pharmaceutical companies waited for vaccine candidates to get closer to the end of the approval process before doing so.
“The pandemic has illustrated both political and market failures in vaccine development,” says Professor Lisa Ouellette, an intellectual property and innovation law expert at Stanford Law School. “Current COVID-19 vaccine prices are rewarding developers with only a fraction of their social value.” (Has anyone clued the politicians in on this?)
That mismatch leads pharmaceutical companies to under-prioritize investment in vaccines relative to other, more lucrative medicines, which ultimately costs lives.
The gaps in incentives for vaccine production begin at the research and development stage. Part of the benefit of vaccine research is that it serves as a kind of insurance, a precaution in the case that an epidemic does happen. But “private firms generally aren’t compensated for R&D spending related to risks that don’t emerge,” says Ouellette.
So, pharmaceutical companies wait and see. They hold off on critical research until ascertaining that a disease has emerged and is likely to cause enough harm to provide a return on research investments. “We have a system in which waiting for demand to increase pays off, as opposed to conducting R&D that may be useful to prepare for or respond to the onset of disease,” says Professor Ana Santos Rutschman, a health law expert at St. Louis University, who added, “By that point, health crises have expanded and lives have been lost.”
More than simply sharing the IP for vaccine development, the bigger issue related to global reach is about manufacturing and distribution. So, why not engage those processes? In truth, more companies able to produce the vaccine from the IP of those creators still need access to capacity for manufacturing and distribution. This means it is not simply drug development from IP but the creation of a more effective value chain.
The alternative might well be the retention of patents with the licensing of the know-how. Covid-19 is an unprecedented and acute challenge to human health globally. While global cooperation offers the best chance for the fastest effective responses, it should only be done by ensuring information transparency and respect for IP rights.
Undeniable Socio-Political Realities
Yes, the U.S., with only 4% of the world’s population, has purchased almost half of Pfizer’s total expected supply in 2021. In fact, 10 countries had gobbled up 75% of the world’s Covid-19 vaccines while people in more than 130 countries had yet to receive a single dose.
Often cited by the "suspenders" as an example of why COVID IP sharing would work are the drugs developed for AIDS that were shared globally. However, that lacks the context of scale. Those suffering from AIDS were not all people in all countries, as is true of COVID-19. As such, absent the suspension of IP, specific solutions for expanding manufacturing have included some instances of pharmaceutical companies transferring the know-how and rights for a vaccine’s production to other companies, such as AstraZeneca allowing the Serum Institute of India and South Korea's SK BioScience to produce its vaccine.
But this time it isn’t a matter of punching out a bunch of pills, a relatively simple process. Covid vaccines require a complex manufacturing process that requires difficult-to-secure ingredients and equipment, meaning there are not enough of these materials anywhere in the world, and competition for it comes down to the prices reflected in supply and demand. So, allowing other manufacturers to appropriate the intellectual property would not increase the supply of the starting ingredients. Rather, it will make it harder and more expensive for the currently approved drug makers to produce more vaccines, as raw ingredients are diverted to new manufacturers with far less efficient production and, as these new companies would then run new clinical trials on copied vaccines, world-wide production of Covid vaccines would decline, not expand.
Knowledge transfer alone will not solve the problem of ramping up manufacturing nor cure the reality that not every country is ready to move forward with an ability to produce and distribute a vaccine.
As previously noted, vaccine manufacturing is a complex process requiring unique equipment for each stage and for each type of vaccine, as well as strict quality standards and highly trained employees. And just because a country has existing manufacturing capacity doesn’t mean it can easily retrofit a plant to produce COVID-19 vaccines.
Vaccine production requires high upfront investments, but there aren’t enough incentives to invest because of uncertainty around long-term sustainability, said Dr. Githinji Gitahi, CEO at Amref Health Africa.
Right now, there are shortages of COVID-19 vaccines globally, but there could be excesses later as more people are inoculated. Rather than giving up IP, the U.S. government can put additional resources behind the immediate development of more manufacturing capability, building facilities to make the starting materials, and buying more of the specialized mixing machines. The Biden administration can also support the donation of more vaccines by protecting U.S. companies from foreign litigation.
The U.S. program could complement global partnerships like the United Nations program Covax, which is already distributing vaccines donated by U.S. drug makers to low-income nations. Low- and middle-income countries are no less deserving than Americans of a vaccine that meets U.S. standards for safety and efficacy.
In fact, Biden administration officials are anticipating the supply of coronavirus vaccine to outstrip U.S. demand by mid-May if not sooner, and are grappling with what to do with looming surpluses when vaccine scarcity turns to glut. So, why the threat to vaccine IP when there are unknowns around the need for vaccines in the future that include the effectiveness against new variants of the coronavirus, the length of protection that inoculation offers, and whether booster shots are needed?
All of this relates to the use of IP by vaccine makers to create the booster shots needed to further immunization and in development of a vaccine to further guard against variants. The truth is any country can build capacity, but if they are not able to manage production to meet demand and distribute accordingly, the reality will be a lot of dormant manufacturing sites.
For example, starting in 2005, the World Health Organization worked to expand production capacity for pandemic influenza vaccines in 14 countries, including Egypt and South Africa, for over a decade. But the high cost of production relative to demand shuttered many plants. When you look at sustainability, it's not such a rosy picture. Many of those facilities are either already shut down or at risk of being shut down,” said WHO Chief Scientist Soumya Swaminathan at a recent conference. The African continent also has segmented markets, with many countries and small economies. Vaccines are often produced in large quantities at low prices, creating the necessity for large markets.
Even without these barriers, there are global shortages around materials, such as vials and stoppers, needed to manufacture vaccines. The U.S. banned the export of filters and bags, among others, to ramp up domestic production. Because of this, scaling up the number of manufacturers fighting for the same supplies might not make sense.
The big question is whether these countries are going to have access to the vials, syringes, and the raw materials when even the existing manufacturers are having problems. In fact, the current vaccine manufacturers are competing over the same number of limited resources. This does not require a post-doc in economics or supply chain management to recognize the potential costs or attendant problems.
Summary
As this article noted, the Quad – a group comprised of the U.S., India, Japan, and Australia that seeks to counter the influence of China – announced a complex financing deal that would enhance manufacturing of vaccines in the Indo-Pacific region where there has been a shortage. The group set a goal of delivering up to 1 billion COVID vaccines to underdeveloped nations by 2022.
Amidst all the noise, the EU has fallen behind in their commitment to provide vaccines to the United Nations for vaccinations of people in poorer countries. As might be expected, when the going gets tough, a donnybrook of sorts breaks out and the supposed EU went from “we are all in this together” to a “grab what you can.” Germany has secured some 50 million Moderna shots and Hungary and Slovakia have turned to the Russian-made Sputnik V vaccine, without an EU approval. And now the new administration in the U.S. wants to give the IP away! Does the U.S. really need to do that? Perhaps, left to hacking Russia, China or North Korea will get it without our capitulation.
If it is not clear to politicians it should be, business executives run American pharma and biotech and China intends to do everything it can to undermine the U.S. in any and all of its businesses. While it is an entirely different conversation, American businesses in China have long understood that access to China and its enormous population comes at a risk if not cost to IP and the outcome is a world more dependent upon China.
China has indicated clearly it will tighten international production chains by employing “powerful counter-measures and deterrent capabilities” that amount to an effort to accumulate IP and exert economic leverage to achieve its political objectives on a global basis. For the U.S. government to give away American pharma IP is nothing less than giving aid and comfort to an enemy.
However, if the current administration follows its own words – that China is the only competitor potentially capable of combining its economic, diplomatic, military, and technological power to mount a sustainable challenge to a stable and open international system – then there can be no sharing of the IP for a COVID vaccine or antibody.
It is not simply a matter of business success, it is a matter of the value of democratic freedoms that enable American businesses to create, develop, and succeed where others do not. Should we apologize for the values of our country that enable success? Is this another version of guilt-inducement for being successful? It should not be. From a strategist’s perspective, the strength of American enterprise is when it is not constrained by political ideology and when success is not something to apologize for, or to give away those intellectual secrets that are competitive advantages.
A U.S. program could complement global partnerships like the United Nations program Covax, which is distributing vaccines already donated by U.S. drug makers to low-income nations. While low- and middle-income countries are no less deserving than Americans of a vaccine, they are similarly deserving of a vaccine that meets quality and efficacy standards.
Yes, we can expect demand for knockoff vaccines to be filled by Indian and Chinese companies that don’t do business with Western drug makers and are eager to exploit America’s advanced technology without paying for it and that will assuredly be unencumbered by American safety standards.
The U.S.-based health charity – CARE – estimates that for every $1 spent on vaccine doses, governments need to spend $5 extra in getting the shots into people’s arms. But the COVAX division meant to help countries prepare for the rollouts have received only $600 million leaving an operational needs gap of $7.3 billion. The World Bank has only committed $2 billion of the $12 billion expected for financing vaccines and strengthening the systems. Perhaps, U.S. and global politicians should impress upon the World Bank the critical need for operationalizing their committed investment.
So it is that patent-breaking politicians are presenting a false choice about the need to give away intellectual property to ensure global public health. The evidence is clear that breaking patents won’t accelerate vaccine production or distribution to poor countries. Pharmaceutical companies are ramping up manufacturing as fast as they can to enable distribution, including in low-income countries.
Rather than giving up IP, the U.S. government can put additional resources behind the immediate development of more manufacturing capability, building facilities to make the drug materials, and buying more of the specialized mixing machines. The Biden administration can also support the donation of more vaccines from U.S. vaccine-producing companies by allowing U.S. companies to retain their intellectual property.
Perhaps, the vaccine makers should argue the retention of their IP is an investment in infrastructure or a means to offset climate change. Clearly, those two areas have the Biden administration’s undivided attention.
All I am left to say is – Hey Joe, c’mon man. Don’t give away our IP.
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Scientists try to overcome the 'valley of death' of vaccines in Brazil
Vaccines candidates against covid-19, Butanvac, the Butantan Institute, and Versamune, from Farmacore and USP, should advance to clinical studies this semester.
BY KEVIN DAMASIO
PUBLISHED TIME: 6 MAY 2021 17:05 ET
Scientists from the Oswaldo Cruz Foundation in Rio de Janeiro open eggs and remove embryos to manufacture vaccines in 1943, a technology similar to butanvac. Despite the history in the production of immunizers, Brazilian vaccines have difficulty in moving from the pre-clinical phase, from development and animal testing to clinical, when there are human trials.
"Let's go forward," célio Lopes Silva celebrated. In January, the biochemist and a team of researchers had just analyzed the results of preclinical studies of Versamune, a candidate vaccine against covid-19. They were confident that they would finally overcome what scientists in the area call the 'valley of death' of vaccines in Brazil: the advancement of laboratory and animal studies for human trials. The project is the result of a partnership between the Faculty of Medicine of Ribeirão Preto, university of São Paulo (FMRP-USP), the Brazilian company Farmacore and the American company PDS Biotechnology.
Lopes is a professor at FMRP-USP, where he coordinates the Gene Vaccines Laboratory of the Department of Biochemistry and Immunology. In 2005, Lopes and Helena Faccioli founded Farmacore, which began in the Supera incubator on the university campus. Today he is a scientific advisor to the company. The biotechnology startup focuses on the development and research of immunobiological products, both for human and veterinary health. "During the incubation phase, we established several technological platforms based on DNA vaccines, recombinant proteins, vaccines vectorized by inactivated microorganisms, among others," he says.
Since then, Farmacore has carried out projects in partnership with lopes' laboratory. They develop, for example, a candidate vaccine against tuberculosis on a DNA platform. This disease results every year in 1.5 million deaths worldwide. The immunizer has succeeded in preclinical studies, funded by the U.S. National Institutes of Health, but human trials have not yet begun.
In early 2020, Pharmacore scientists analyzed the pandemic scenario, the first immunopathology results of candidate vaccines against covid-19 and the technology they already had in the company. They then decided to use a platform called Versamune, licensed four years before PDS Biotechnology.
Then, Farmacore, FMRP and PDS signed a contract with USP to conduct proof-of-concept trials and pre-clinical and clinical studies. In May, they requested recourse to the Ministry of Science and Technology (MCTI). On August 21, they received from the folder a contribution of R$ 3.8 million. Added to the resources committed by Farmacore and PDS, it was enough to start the project.
The vaccine is composed of the carrier Versamune and an antigen – the S1 protein of Sars-CoV-2. The carrier is formed by a single lipid molecule called Dotap, a fat that enveloops the antigen. "This carrier is a great immunomodulator," lopes explains. "It, by itself, activates the immune system, especially in the production of interferon type 1. In any viral infection, this is one of the most important molecules to stimulate in the immune system. This causes other cells to be activated, such as natural killers, natural killers."
In August, scientists went to the lab bench to check for interaction between the carrier and the Sars-CoV-2 antigen. They tested several proteins of the virus and elected S1, because it was the mostimmunogenic, producing both neutralizing antibodies, as well as polyfunctional CD8 and CD4 T cells. In the physical-chemical analysis of the compound, "the results were excellent, there is interaction," lopes recalls. Thus, the team proceeded to the development of the vaccine formulation, which proved "very stable at refrigerator temperature and easy to produce".
Coronavirus connects to the human cell through the spike protein, which is divided into two subunits: S1 and S2. In part S1 is the RBD domain, through which the virus binds to the host cell receptor. "We don't need to use the entire spike. Domain S1 contains all the elements to develop an immunity that can block the connection of the virus with the host cell, in addition to stimulating cellular immunity," lopes notes.
Every vaccine has a carrier, either viral or nanoparticle. In the case of AstraZeneca/Oxford immunizations, the Gamaleya Institute and Janssen, the carrier used is a viral vector. Moderna, NovaVax and Pfizer/BioNTech adopt a nanoparticulate lipid carrier – similar, but more complex, than the system adopted by Versamune. "Ours is a nanoparticle, only we put the recombinant protein straight into the cell. So there's one less step," Lopes says. "Once it enters the cell, it activates the entire immune system. In addition to the adjuvant's own immunity, it will also stimulate the production of neutralizing antibodies."
With success in the initial stage, the researchers left for preclinical trials on animals at the end of September. The immunogenicity study was carried out in mice, in which they analyzed humoral (neutralising antibody production) and cellular (CD4+, CD8+ lymphocyte scans and dendritic cell activation). According to Lopes, pre-clinical studies have shown that Versamune is capable of stimulating these two immune system responses. "It fantastically stimulates cytotoxic CD8 T lymphocytes, which recognize infected cells and destroy them," lopes says. "When Sars-CoV-2 enters the cell, it has the mechanisms of inactivation of interferon type 1, which is a weapon that disables the immune system. Our vaccine activates it and overcomes this war between deactivation and activation. It is an important and differential factor." Then scientists conducted a toxicity assessment in order to identify whether the vaccine is safe.
"We are managing to overcome this 'valley of death' because there was such cooperation. Who knows, in the future, we'll be able to have more independence. "
With positive preclinical safety and immunogenicity data, the researchers decided to seek the National Health Surveillance Agency (Anvisa). The agency is responsible for authorizing or rejecting trials that have a regulatory purpose, that is, that will require registration of vaccine or medication. After three meetings, the researchers from Farmacore and FMRP-USP submitted the Clinical Drug Development Dossier (DDCM) in order to obtain agency's support for the performance of phases 1 and 2 trials from Versamune. They are still preparing the Clinical Study Dossier, in which they must detail the test protocol, with delivery expected by the end of May.
Regulatory demands
Anvisa takes into account four main aspects in its analysis. In the case of vaccines that will be administered for the first time in humans, the first point analysed is data from non-clinical studies carried out in animal and laboratory models. "What we want to see is basically whether these studies have shown safety, especially with regard to toxicology and possible adverse events – hepatotoxicity, liver attack, kidney, anything that might bring an alert," explains Gustavo Mendes, general manager of Medicines and Biological Products at Anvisa.
The regulatory agency also requires information on the history of vaccine development. "Versamune is a technology unlike any we have approved so far. Her proposal is a synthetic peptide, that is, the coronavirus protein itself, made in a laboratory way, is applied to the person to generate immune response", mendes exemplifies. "Understanding this biotechnology is an important part of our assessment."
The applicant also needs to submit a protocol of the clinical study he wishes to carry out. Information such as how many volunteers will participate in the trial, what research centres are, and how the statistical approach will be to reach safety, immunogenicity and efficacy data.
In addition, it is necessary to demonstrate good clinical practices. This aspect is related to the degree of reliability and traceability of the data that will be generated. "The reports, the clinical record, the documents that accompany the study participants," Mendes continues, "all of this has to be traceable and follow international regulatory standards so that when we do the evaluation for vaccine approval, we have confidence that that study happened and actually followed the rules."
The Butantan Institute has also initiated the application for an application for clinical studies of its own vaccine. Butanvac is produced in embryonic egg and adopts viral vector technology, with the inactivated virus of Newcastle Disease, a pathology that infects birds. "This vaccine will be fully produced here. We will not depend on the import of any insum. A technology that already exists, the same used for the production of the flu vaccine," said Dimas Covas, Ceo of Butantan, in the announcement of the candidate vaccine on March 26. The institute plans to conduct the study in humans 20 weeks later authorization, which will include participants over 18 years. Anvisa has already received both dossiers with the history and protocol of the clinical study, but asked for further clarification to follow up the technical analysis, such as data and information on vaccine quality control and details about the clinical protocol.
"These vaccines have won a stage that has been very critical in production in Brazil, which is to leave the pre-clinical study to seek authorization from Anvisa for the clinical study," notes Viviane Boaventura, a professor at the Federal University of Bahia and a member of the Department of Clinical Immunology of the Brazilian Society of Immunology (SBI). "They have already advanced this phase and have the material ready to do human testing. That's great news. But we really need, as a strategy to confront and develop vaccine technology in the country, optimize this operation, so that we have more candidate vaccines reaching this same stage."
"Are we arriving late? It might be. But this disease is here to stay and, with these new variants emerging, we will have a very important role."
Boaventura considers that international partnerships are fundamental in this initial phase of development in the country. "We are managing to overcome this 'valley of death' because there was such cooperation. Who knows, in the future, we'll be able to have more independence. But partnerships will always happen and will always be welcome. Research in the world today is international."
In addition to Versamune and Butanvac, there are other Brazilian projects in advanced stage in the pre-clinical stage. The Federal University of Minas Gerais develops the Spintec vaccine,which adopts the chimeric protein platform, and announced on April 28 that it will receive R$ 30 million from the city of Belo Horizonte (MG) to enable the start of clinical studies. At the Heart Institute of the Faculty of Medicine of USP, a team coordinated by immunologist Jorge Kalil Filho is finalizing the preclinical tests of a nasal spray vaccine that had an investment of R$ 20 million from MCTI, R$ 5 million from the Research Support Foundation of the State of São Paulo and R$ 104 thousand from USP Vida.
New aspects of studies
According to Oxford University's Our World in Dataplatform, 7.9% of the world's 7.79 billion received at least one dose of covid-19 vaccines by the last Wednesday, May 6. The first vaccines against covid-19 approved and administered currently in Brazil were submitted to tests that follow the gold standard considered by Anvisa. These are the double-blind and randomized studies, in which half of the participants receive the candidate vaccine and another group, a control substance – or placebo, or a vaccine for another disease. However, the second generation of vaccines against covid-19 will need different methods. "With the expansion of vaccination and the fact that we already have approved vaccines, this situation becomes a little more complicated, especially because of the ethical aspect," mendes says. "What changes for Anvisa is the way the study is designed."
"The biggest challenge is that with the fact that we have safe and effective vaccines available, the clinical trial can no longer be done with placebo, as for initial vaccines. It wouldn't be ethical," says Denise Garrett, an epidemiologist and vice president of the Sabin Vaccine Institute. "The new clinical trials now have to be what we call non-inferiority studies, to show that the new vaccine is not inferior. These tests require more sampling and are much more expensive." For Garrett, new covid-19 vaccines need to go beyond being as or more effective than the current ones: they should be "cheaper, easier to store and distribute," as well as "expand the immune response, including protection against emerging variants."
Given the calamity in health services around the world, with overcrowded hospitals, the priority of studies of the first vaccines against covid-19 was clear: decrease disease worsening, hospitalizations and deaths. For new immunizers, Boaventura attaches a "gigantic importance" to the focus on preventing infection, a feature that will help control the pandemic in the long run. Preventing infection means that the virus cannot connect to the cell, so the person does not develop the signs and symptoms of the disease. Protection against the disease happens when the virus still connects to the cell, but is soon neutralized by the immune system.
"When you administer any vaccine, not only covid, we know that there is one group of people who respond very well and another, not, for genetic, background or health conditions that leave the defense system suppressed," reflects the immunologist. "We need these people to be indirectly protected by reducing the circulation of the virus. And we will only reduce the circulation of the virus very effectively if vaccinated people no longer have the ability to transmit or become infected."
This strategy makes the clinical study more detailed, expensive and time-consuming, Boaventura continues. "Covid may give symptomatic or asymptomatic disease. A study aimed at preventing infection has to systematically keep swab from these people for a long period, to assess, even without symptom, whether there are any viruses in these people's airways."
Clinical trials
Célio Lopes detailed to the report the planning for the clinical trial of Versamune. Like the first covid-19 vaccines already approved, phases 1 and 2 will occur simultaneously. It will take 360 study participants to attest to the immunogenicity and safety of immunobiological scans in humans. The tests should take place in a single research center in the state of São Paulo, probably in the state capital, and will be applied in four cohorts, or groups of volunteers. "We intend to apply two doses – low and high – in two experimental groups, aged 18 to 55 years and 56 to 75," he says. Lopes hopes that if they get an anvisa's agreement, the work will begin between June and July. The study is expected to last at least a year, with the possibility of opening the results after three months for preliminary analysis of safety and efficacy. "In this design that we did, this range of 56 to 75 is already impaired, logically," lopes notes, taking into account the immunization campaign against covid-19. "As a clinical research unit, we are already working to redo these phases."
While preparing the documents pending submission to Anvisa and awaiting authorization, Lopes already plans the next step: phase 3. He estimates that the study will include at least 20,000 participants, which would require a large batch of the Versamune vaccine. With this, they work on the implementation of the technology by a national pharmaceutical company, so as not to depend on the import of the active pharmaceutical ingredient, the IFA. This would also allow a large-scale production so that in December, when phase 3 is over and if the results are satisfactory, the immunization of the population with Versamune can already begin in January or February 2022.
"For phase 3, we won't have placebo, so we have to change the scope. We're going to do a comparative clinical trial with another vaccine that's closer to our profile, which would be maybe pfizer's, or even AstraZeneca's. And then we'll see the efficacy studies," lopes says. "We will do comparability or non-inferiority studies to see if it gives more or less similar results, for example, to AstraZeneca, about 70%, or, if it is pfizer,, around 90%. Then no individual will go unvaccinated."
The MCTI has committed to two more contributions for the development of the Versamune vaccine. For phases 1 and 2, the ministry will allocate approximately R$ 30 million. For phase 3, it will be R$ 282 million. However, at the end of April, President Jair Bolsonaro blocked R $ 272 million from the budget of the folder and vetoed another R $ 371 million. Of the amount vetoed, R$ 200 million would be allocated to Versamune's studies.
National Geographic asked MCTI if the veto would make it impossible to support clinical studies and whether the portfolio already has any alternative to funding, but there was no response until the publication of this report.
"We are still looking at the funding scenario for clinical studies. What we are sure is that from some source we will have theseresources," lopes said.
Investment and autonomy
"Are we arriving late? It might be. But this disease is here to stay and, with these new variants that are emerging, we will have a very important role", lopes considers. He reflects that brics bloc countries - China, India and Russia - have already developed their own vaccines. Brazil and South Africa do not, due to a technological delay that impedes development at all stages. "What we're doing is making a very significant contribution to national science and technology."
In addition, Lopes believes that the vaccine will be enough to protect against variants of concern, by stimulating cellular immunity, but that there is also the possibility of changing the antigen to adapt it to others that may emerge. "It's what Brazil needs right now. Other coronaviruses may arise, other countries, logically, because we are stirring a lot in Brazilian biodiversity", he analyzes. "We will be a little more adapted, having our national product, with a production company here, with all the technology. And we make a contribution to Brazil not to depend exclusively on imports of products, vaccines, the market, competition."
According to Boaventura, from SBI, three aspects are fundamental for Brazilian science to advance from the current level, in which researchers are unable to proceed to the clinical studies of their candidate immunizations. First, to create research and development platforms disseminated throughout Brazil, with the objective of facilitating the realization of pre-clinical studies in animals. Secondly, to promote partnerships "so that products leave the laboratory and those that actually show safety and protection in animal model pass to the clinical trial". Finally, the support and financing of studies using new technological platforms, such as messenger RNA technology adopted by Pfizer/BioNTech and Moderna vaccines.
"Brazil cannot miss the tram of this boom of innovation and discovery in the area of vaccine. It really needs to invest, so that our scientific community is at a level of creativity close to what happens in other countries", warns the immunologist. "It is a crucial moment for Brazilian science in the development of vaccine and these platforms. If we don't follow the floor of the carriage, we could lose a very important timing to have autonomy in the future."
Link to story
Older article from 03/26/2021, sorry if already posted but it gives some background details.
Understand point-to-point Versamune, a vaccine against Covid-19 funded by the federal government
Immunising uses recombinant protein from Sars-Cov-2 itself, which causes Covid-19 with nanotechnology. Application for clinical trials was sent to Anvisa on Thursday (25).
By Vinícius Alves and Thaisa Figueiredo, G1 Ribeirão Preto and Franca
26/03/2021 18h42 up-to-date a month ago
The federal government announced, on Friday (26), that was filed with the National Health Surveillance Agency (ANVISA) the request for authorization for clinical trials in humans of Versamune®-CoV-2FC, potential candidate for the Brazilian vaccine.
The announcement was made by Minister Marcos Pontes, who said that the study is supported by the Ministry of Science, Technology and Innovations, through hiring a research group.
The development of the immunizer is coordinated by researcher Célio Lopes Silva, from the Faculty of Medicine of Ribeirão Preto (SP), University of São Paulo (USP), in partnership with the Farmacore group and PDS Biotechnology Corporation.
"This is a new vaccine, which has the potential to activate the entire immune response and control Sars-Cov-2 infections very well," Lopes Silva told The National Newspaper.
In November 2020, Pontes and the then Minister of Health, Eduardo Pazuello, were in Ribeirão Preto to evaluate the research. At the time, without giving details, Pazuello said that the visit had been "champion".
In this report, you will understand, peer-to-peer, some details about Versamune:
Why is Versamune relevant? Does it make sense to have a vaccine for months?
When will the tests begin? Who's going to be able to apply?
Are the predictions of completion of the studies realistic?
What will the vaccine be like? What technology is she going to use?
Will the vaccine be safe?
How much will be invested by the Ministry of Science, Technology and Information?
1.Why is Versamune relevant? Does it make sense to have a vaccine for months?
The director of Fiocruz, Rodrigo Stábile, says that the development of the immunizer in Brazil shows that the country has competence to do science and technology, especially for public health.
"We know that for us to have an enrichment, autonomy and national sovereignty, we have to invest in the economic-industrial complex of health. A strong science and strong scientists we have. What is missing is an investment to have large-scale production plants of these vaccines," he says.
National production would exclude the country's dependence on intake from China or India, for example, but Stábile considers that manufacturing in Brazil depends on investments in a specific production plant, which has a high cost.
"It is a production plant that is not one of the cheapest. You need to have large fermenters, large cell growers to be able to produce such a vaccine in good manufacturing practices. It's not an easy-to-employ vaccine in terms of good manufacturing practices, but we have the know-how for that."
The researcher says that although the studies are promising, they demand more resources from the federal government, mainly because Latin America lacks production plants.
For the infectologist, professor at Unicamp and consultant of the Brazilian Society of Infectious Diseases, Raquel Stucchi, the possibility of the arrival of new vaccines increases the chances of a greater and more agile scope of immunization in an upcoming campaign.
"Now, in this short period of time, it will not be these vaccines. We need those that are already on the market to be able to vaccinate as soon as possible. Possibly, against Covid, we're going to have to get vaccinated with a certain frequency. So the more vaccine producers we have, this is very desirable, this is very good. We have vaccine with our production gives us autonomy and is a guarantee that we can always be vaccinating, in a timely manner, our population."
Research coordinator at USP, Célio Lopes Silva says that Versamune®-CoV-2FC has the ability to modify itself to combat, also, the new variants of coronavirus that are already in circulation or new ones that may arise.
"If some of these variants, now mutants, are emerging, and our vaccine eventually does not have an efficiency of 100%, we can also change our antigen and we can adapt this technology just as all the big companies are running. (...) We are also thinking of another strategy," he explains.
2. When will the tests begin? Who's going to be able to apply?
Anvisa reported that the analysis of the application will take into account the study proposal, the number of participants and the safety data obtained so far in pre-clinical studies that are conducted in laboratory and animals. The deadline for evaluation is 72 hours.
According to Pontes, the developers of the vaccine began on February 13 to send documents to Anvisa and, at 13:23 on Thursday (25), they requested authorization for clinical trials phases 1 and 2.
"Phase 1 is a test that will see if the vaccine is safe, if it does not cause any harm to humans. Phase 1 is essentially intended to test safety if you will have adverse reactions. It's made in a few people, about 100 people, out there. Phase 2 extends a little. It can reach 800 people. She is still excelling in safety, if it will not cause serious adverse reactions, but she is already starting to see if it wakes up our immune system", explains the director of Fiocruz, Rodrigo Stábile.
The Pharmacore reported on Friday night that the 360 volunteers from phases 1 and 2 will be people aged between 18 and 55 at first, and then 55 to 75 years. At this stage, it is mandatory to have placebo.
The tests will be done in a clinical center in the city of São Paulo, where the vaccine is expected to be produced on a large scale later. In phase 3, the study will extend throughout Brazil, with up to 30,000 volunteers expected.
"We would love to prioritize day-to-day workers. Workers in industry, commerce, service, utilities, such as transportation, who are the most susceptible people who have to be on the street every day and are more susceptible to contracting the disease," said Helena Faccioli, ceo of the company.
Célio Lopes Silva, a researcher at USP, explains that there is no study yet for the application of the vaccine in children and pregnant women.
"We need to finish the phase 1 and 2 clinical trial, then in phase 3, depending on the results, we can include a group of children at different ages," he says.
3. Are the predictions of completion of the studies realistic?
The federal government reported that the company has already submitted to Anvisa promising and robust preclinical data in tests already conducted on rodents with the S1 protein associated with the vaccine platform.
Helena Faccioli expects the studies to be completed between February and March 2022, when she believes the vaccine will have emergency use approved by Anvisa.
"The idea is to start with at least 40% of the demand that exists today for vaccine for the population. I'd give you 400 million doses a year. We are thinking of first supplying the demand of the national market. Our priority is to vaccinate workers in Brazil. If there is leftover, if there is industrial capacity to feed the other countries, you will be welcome," he says.
On the same day that the federal government announced the Versamune protocol, the Butantan Institute said it will ask Anvisa to release Butanvac clinical trials.
For the director of the Brazilian Immunization Society (SBIm), Renato Kfouri, the enthusiasm for a 100% national vaccine is great, but caution is needed.
"You can't guarantee that they'll get licensed, studies are starting. We have almost a hundred vaccines in clinical phases, we have almost 200 vaccines registered in the world in pre-clinical studies, 100 more or less in clinical studies and there, in the end, a dozen of these will become licensed products. Let's hope the studies go well."
Similarly, Kfouri warns that consideration is needed when mentioning deadlines for large-scale applications. "Promising delivery, vaccination start date of a product that has not even been tested is somewhat unrealistic. We can't start talking like that about these vaccines that start testing now."
4. What will the vaccine be like? What technology is she going to use?
Pharmacore and PDS Biotech said the vaccine is the combination of a recombinant protein from Sars-Cov-2 itself, which causes Covid-19, with the nanotechnology of the Versamune® platform, a patented technology for the activation of immune system T cells and antibody production.
"The two associated components stimulate the neutralization of the virus when it enters the body. If it overcomes this barrier, the two complexes together will stimulate the production of T cells in the immune system that will fight, will kill infected cells and not allow the person to get sick, and offer long-term protection," says Helena Faccioli.
The solution under study has a delivery system – innovation developed by the American company PDS Biotechnology – that takes these substances to lymphocytes.
"So if eventually the virus enters the cell, in a way, we have antibodies that block its entry, but if it enters, we have lymphocytes that kill the infected cells," says researcher Célio Lopes Silva.
5. Will the vaccine be safe?
The ministry said that, to date, the results of non-clinical studies of Versamune (toxicity and immunogenicity) demonstrate the ability to activate the entire immune system – humoral, cellular and innate immunity, induce immune memory and long-term protection.
Currently, Brazil applies the National Immunization Plan (PNI) with the Astrazeneca/Oxford and CoronaVac vaccines. According to Kfouri, production is moving towards self-sufficiency.
"Those are realistic promises, right? It's not a question of 'are we going to work out?' They've worked out, right? They are vaccines already used all over the world, they are vaccines already with part of the production being made here in Brazil and the total production will go", he says. "The transfer contract is exactly that for by the end of the year: Bio-Manguinhos will be producing Oxford and Butantan being producing Coronavac. 100% Brazilian, regardless of pharmaceutical inputs from outside, which accredits us to be self-sufficient, to be exporters, not to depend on the international market, to supply Brazil and other countries", he says.
6. How much will be invested by the Ministry of Science, Technology and Information?
According to the federal government, the ministry has guaranteed R$ 200 million for funding clinical studies to continue the development of Brazilian vaccines. The resources were secured after the adoption of the 2021 budget.
In G1,The Pharmacore reported how much was spent in the pre-clinical phase and the investment projections of phase 1, 2 and 3.
Pre-clinical: R$ 3.8 million
Phase 1/2: estimate of R$ 30 million
Phase 3: R$ 300 million
Link to 03/26/21 article
Candidate for Brazilian vaccine against Covid, Versamune will be tested in June and is expected to apply in December, says CEO of Farmacore
Request for clinical trials of the immunizer will be delivered in full to Anvisa by the end of May. Funding from the Ministry of Science is secured, according to the CEO.
By Pedro Martins and Rodolfo Tiengo, G1 Ribeirão Preto and Franca
05/05/2021 05h00 up-to-date 5 hours ago
A candidate for the Brazilian vaccine against Covid-19, Versamune will begin testing in humans in June and the application in the general population is scheduled for December, Helena Faccioli, CEO of Farmacore, the biotechnology startup that develops the immunizing with the support of the University of São Paulo (USP) in Ribeirão Preto (SP) told G1.
The CEO said on Tuesday (4) that the three phases of the clinical study of Versamune will cost R $ 340 million and will be funded by the Ministry of Science, Technology and Innovations. Although the federal government has cut and blocked R$ 663.8 million from the portfolio, when sanctioning the 2021 budget, the immunizing tests will not be harmed, according to Faccioli.
Wanted by G1, the Ministry of Science and Technology did not comment on the case.
In this report, you will understand, point by point, the next steps that Versamune will have to take until it is made available to the population:
What is missing for Anvisa to approve the start of Versamune testing?
How will Versamune's human tests be done?
When can Versamune be applied to the population?
What are the differences between Versamune and the other vaccines already in use?
How much does it cost and who will pay for versamune testing?
1. What is missing for Anvisa to approve the start of Versamune testing?
The Pharmacore filed on March 25 the application for authorization for versamune tests on humans. Two days later, the National Health Surveillance Agency(Anvisa)responded that it needed more documents to approve them.
The CEO of Farmacore, Helena Faccioli, said that the remaining documents are quality control reports of the batch of doses that will be used in the tests.
The production, made by a partner in the United States, was delayed by two months. With this, the documentation should be delivered in full to Anvisa by the end of May.
"Due to the lack of availability of material and equipment, we had a delay in the production of this lot and, consequently, in the reports. You have to do quality control of each stage of production, to ensure purity, sterility and that the vaccine bottle is intact", says Faccioli.
After submitting the documentation, Anvisa has 72 hours to approve or not the clinical study. The CEO says that if the approval is immediate, The Pharmacowill ask the U.S. partner to send the doses immediately to Brazil.
The deadline for delivery of the lot is around two to three weeks. With this, it is estimated that the application in volunteers begins by the end of June.
2. How will Versamune's human tests be done?
The tests will be divided into three stages, as with any vaccine. The first two phases will have 360 volunteers – 240 will receive the immunizer, while the rest will receive a dose of placebo, i.e. without action.
For this public, the company ordered 624 doses, considering the two necessary for immunization and a reserve of 30% produced in case there are failures in applications. The vials will come with five doses, each with half a milliliter.
The applications of the first two phases will take place in São Paulo (SP),at the Heart Hospital, the HCor. The study will be coordinated by researcher Célio Lopes Silva, from the School of Medicine of USP of Ribeirão Preto.
Volunteers will be able to register to participate in the tests through a website. The target audience is people over 18 years of age, without chronic diseases, who have not been infected or vaccinated against coronavirus since the beginning of the Covid-19 pandemic.
The pre-selected will undergo a screening in the HCor. In addition to being reevaluated, volunteers will take an RT-PCR test, which identifies the virus by samples collected in the nose and throat, and a blood test, so that there is confirmation that they have never had contact with Sars-CoV-2.
The first phase will have a smaller group of volunteers, whose number of members has not yet been defined by the Pharmacore. In it, the researchers will analyze what are the possible serious adverse effects caused in the short term by the immunizer.
From the second phase, it will also be evaluated what is the immune system response of volunteers and what should be the concentration of the immunizer to generate the ideal effect. Two different concentrations will be tested.
The third phase should have 20,000 volunteers, not only from the capital of São Paulo, but from all over the country. The public able to volunteer can be changed, with the possibility of including people with chronic diseases and other age groups, according to the CEO.
In the third phase, safety, efficacy and immunogenicity will continue to be analyzed. However, doses of placebo will not be applied to volunteers, unlike those with other Vaccines against Covid-19.
"When we made the initial proposal for Versamune, I could still use placebo, but now it's complicated, because there are already vaccines available and people immunized, so we're going to have to review that with Anvisa," faccioli says.
The researchers will define, with the support of Anvisa, whether the effectiveness of Versamune will be analyzed by protocols of non-inferiority or superiority in relation to other vaccines already in use, such as CoronaVac.
"In the non-inferiority model, half of the volunteers are vaccinated with Versamune, the other half with a reference vaccine, and Versamune cannot have a lower efficacy. In the superiority, Versamune would have to have a higher effectiveness than the other", explains Faccioli.
3. When can Versamune be applied to the population?
The CEO of Farmacore, Helena Faccioli, estimates that, in an ideal scenario, without any intercorrence, the first two stages of the clinical study will be closed until September. The plan is to start the application in the third phase volunteers.
The third phase, in turn, should be closed by December, when The Pharmacore plans to ask Anvisa for authorization for the emergency use of the vaccine,as did the Butantan Institute when it tested the effectiveness of CoronaVac in the country.
In parallel to clinical trials, Farmacore already plans to start the production of commercial lots in Brazil,so that, if there is authorization for emergency use, the application of Versamune can begin as soon as possible.
"If all goes well, by the end of the year we can start vaccinating. You have to start producing commercial lots already. It's a risky investment, but if we expect to finish each test step to start producing the doses, it would take years," faccioli says.
4. What are the differences between Versamune and the other vaccines already in use?
Versamune combines the protein that coronavirus uses to invade human cells, which induces the production of antibodies, packaged in a nanoparticle that activate the T cells of the immune system, capable of inducing immune memory.
"Versamune not only induces the production of neutralizing antibodies, which is the basic principle of vaccines being used. It has two mechanisms: antibodies and T cells, which generate long-term immunity in the body," explains the CEO of Farmacore.
The CEO adds that, according to scientific literature, vaccines with the same technology have already generated immunity for up to twelve years. It is not yet possible to estimate, however, an exact time frame for the duration of versamune protection, as it has not yet begun to be tested in humans.
Professor at USP Célio Lopes Silva, who coordinates clinical studies, adds that Versamune has the ability to modify itself to combat, also, the new variants of coronavirus that are already in circulation and new ones that may arise.
5. How much does it cost and who will pay for Versamune testing?
Minister Marcos Pontes reported in March that the Ministry of Science, Technology and Innovations had the guarantee of R$ 200 million in the 2021 budget for the financing of versamune's clinical studies.
In a recent internet broadcast before the 2021 budget sanction, Pontes indicated, alongside President Jair Bolsonaro (no party), that the survey would cost R$ 340 million, with R$ 30 million allocated to the first and second phase and R$ 310 million to the third stage.
Pontes also said he expected these resources to enter the government spending forecast for 2021. Following, not to mention specific cuts for Versamune, Bolsonaro stated that all ministries would face resource restrictions.
The law that provides for spending for 2021 was sanctioned in April by the president with vetoes and blockades of about R $ 29 billion, which includes R $ 663.8 million from the Ministry of Science, Technology and Innovations, with the justification of complying with the spending ceiling.
Of the total contained of the Ministry of Science, R$ 291.4 million are from vetoed resources, that is, definitively withdrawn from the budget, and R$ 372.3 million are from blocked funds, which can return to the scope of spending throughout the year.
After the budget was published, also without directly mentioning Versamune, Pontes said he would meet with his team to assess which projects could be continued in the face of reductions imposed by the federal government.
"There are certain types of projects that without a budget have a gap, and this gap kills the project, either because it comes out of the window of opportunity, or because you do not have continuity of research," he said, in an internet broadcast, on April 24.
In a new transmission on Thursday (29), Pontes advocated the development of national vaccines to facilitate the availability of immunizers in the face of a global scenario threatened by new variants of coronavirus.
"That's my whole fight I keep talking about budget. People say, 'you're too boring to talk about budget all the time.' But it's not for the Ministry of Science and Technology. This budget is for Brazil as a whole," he said.
When questioned by G1, Farmacore CEO Helena Faccioli said versamune's clinical trial plans follow as planned.
"This cut did not reach us, but there has already been a recomposition of the money. There was an announcement from the president that he would not release what the ministry needed. Immediately, the ministry acted to seek from another source. Where he's going to get it, we don't know. The project is being touched. Our planning remains the same," he said.
Link to story
Saw that happen with $pavm from yesterday to today. Let's hope pdsb has staying power.
No way pdsb stops at $12 if they have positive data. We have less than 3 weeks to find out what is in the ASCO abstract. If better than expected, market cap could easily jump to $500 million and higher which implies a price 4 times current levels. $500 million market cap is still low priced for an early stage oncology company. I can easily see this at a billion plus in the next few months if not sooner depending on ASCO data.
Add to that, covid program and coming announcements. We should get Anvisa news any day which could green light our p2 trial which should start this month. 2-3 months later and we should get trial results and hopefully the start of p3. Assuming all goes well, these 2 data points could add another $500 million and more to our market cap.
By year end we get data on our other 2 oncology programs plus additional NCI data Add to that data results of P3 for covid. If any/all of these are positive, we could have a market cap in the several/many billion of dollars. Stuff financial dreams are made of and best of all, less than a year for it to play out.
You, me and every other pdsb investor :^)
Brazil is screwed and needs to show they are doing something. PDSB appears to be their best bet right now. Unfortunately when dealing with a psychopath, you can never truly anticipate what they will do. Hope the govt in Brazil is able to keep things under control. We will see.
Best thing is, pdsb is not just covid, the real money is in oncology and we will find out preliminary data in JUST 3 WEEKS. Crazy, if news is better than expected, pdsb will be well into double digits on the news on 05/19/21.
Keeping fingers crossed. All signs point to positive data imo.
You can guarantee they will do a stock raise this year because every development stage bio does a raise whenever they can, not necessarily when they actually need it. They don't need the money this year or next but they will and if market conditions are right, they will do a raise. We may not think it is right but if management sees what they think is a good time, nothing we say will matter.
That said, pdsb burns very little cash annually. They have been great at generating non dilutive cash through investigator sponsored trials and I believe (hope) they will continue to do so going forward. They know what will be presented at ASCO in early June and know what the abstract will show in less than 3 weeks. I really don't anticipate a raise before then because I am very optimistic the ONLY reason we have an ORAL presentation is because the data is better than expected. Assuming I am right, the next raise will come well into double digits and dilution will be minimal.
On top of the known upcoming ASCO news, we could/should get Anvisa news any day. Even though it is Brazil, assuming we get approval to start the trial, we are off to the races.
PDSB has a market cap of less than $150 million. Any good news drives this to half a billion to a billion dollars almost overnight. That translates into $20-40/share from $5 and change. Crazy to think these types of returns are possible in only a few weeks/months. Looking out 6-12 months and you can easily see a case for 2 billion or more market cap with the right news. That is nuts and possible.
Granted, the likelihood is low based on experience of other companies but right now, based on what we know, the above is definitely possible. Today's investors can get rich off pdsb if the science proves out.
GLTA. It is my 3rd largest investment at the current time and I believe in months it will be my largest investment based on future growth that could come in an instant. HODL
I agree, the lack of positive reaction to today's news was disappointing. I guess yesterday's move must have been related to the ASCO presentation. There were some who realized it yesterday while some of us, like me, needed to have the obvious pointed out to them.
I can't think of a reason that PDSB would have gotten an oral presentation without it being very good and positive results. Maybe I am missing something obvious but considering this is a small trial from a relative unknown, why else grant a coveted Oral Presentation unless it is good. If it were bad to just OK, then I would think it would be a poster presentation. Not that poster presentations are necessarily bad, but in this case, I can't think of it being anything but very good since it is an Oral Presentation. I hope I am right and we only have till 05/19/21 to find out when the abstracts are released.
Just think, any day now and we will find out the decision from Anvisa. Hope Farmacore submitted a clean package and we get approval with the first go. When that happens, I can't see the street not bidding us up substantially. 2 potential transformative catalysts coming by 05/19/21. GLTA, I think this is going to be huge.
I couldn't agree more. Just yesterday I was talking with a friend and told him he should buy a few thousand shares to pay for his kids college. I told him there is always a risk to investing but this has the best risk/reward of any stock that I know of where you will know within months if it will be paying off in such a short period of time.
Who knows, next week could bring double digits if Anvisa approves the start of the trial. In less than 2 months we get ASCO presentation where that could bring it to $25-50 with good data. It's totally incredible the explosive potential. Every investor should read the PDSB white paper on their site.
Great new article courtesy of Twitter. Reminder that at $100/share pdsb will be valued at slightly more than $2 Billion which is cheap compared to other biotechs. IF and I say IF, results are what we hope, a year from now we will be looking at many hundreds of dollars/share.
One of the interesting things is Frank is downplaying the Covid trial by saying drug will be available in 2023, not 2022 as their partners in Brazil are saying.
Click for link
Researchers await release to start tests of the vaccine against covid-19 developed at USP in Ribeirão
Versamune has already demonstrated safety for animals and has the ability to activate the entire immune system; the vaccine is developed and produced by the consortium between Ribeirão Preto School of Medicine, Farmacore and PDS Biotechnology
The National Health Surveillance Agency (Anvisa) received the request to start the clinical trial phase in phases 1 and 2 of the Versamune vaccine last Thursday, March 25. The immunizer against covid-19 is a production of the consortium formed by the Faculty of Medicine of Ribeirão Preto (FMRP) of USP, with Farmacore, brazilian startup responsible for technological development, and PDS Biotechnology, which licensed to Farmacore the adjuvant/carrier system of the vaccine formulation.
The work is being coordinated by Professor Celio Lopes Silva of the Department of Biochemistry and Immunology of FMRP and has the support and funding of the Ministry of Science, Technology and Innovations (MCTI). In the first phase of the clinical trial, the immunizer will be applied to 360 volunteers and researchers estimate to complete phases 1 and 2 between three or four months beginning in May. Phase 3, on the other hand, is expected to have 20,000 volunteers in several states of Brazil.
The prediction is that the entire clinical study will be completed between 9 and 12 months, that is, the vaccine developed at USP in Ribeirão Preto should be available to the population in early 2022. On Saturday, March 27, Anvisa requested the results of quality control of the materials and the pre-clinical trial, which are in the process of being finalised by the consortium.
"The results of non-clinical studies have shown that it is safe for animals and, unlike other vaccines, it has the ability to activate the entire immune system that prevents not only the entry of SARS-Cov-2 into the cells but also kills already infected cells. We believe that the immunizer generates an immunological memory of up to 12 years", says Professor Célio Lopes Silva.
In addition, says the professor, this vaccine induces long-term immune memory; it is simple and safe (does not contain inactivated viruses, viral particles, traditional and complex adjuvants, DNA, mRNA); has good stability and ease in production and distribution strategies; it has technological facilities so that it can be fully produced in Brazil in the phases of mass vaccination; and allows establishing a national technological base to help overcome future challenges of new scenarios that can significantly impact the health of the population.
The researchers produced a vaccine formulation composed of SARS-Cov-2 antigen S1, obtained in the recombinant form, and associated with a lipid nanoparticle called Versamune that is used as a carrier/adjuvant vaccine. This formulation composed of S1 and Versamune induces activation of humoral immunity (activation of B lymphocytes for the production of high levels of neutralizing antibodies that prevent the entry of the virus into the cells), cellular immunity (activation of CD8 t lymphocytes and CD4 T that eliminate infected cells) and innate immunity (activation of the ifn signaling pathway type I, which is critical to keep the immune system activated and the generation of sustained adaptive immune responses against viral infections. In addition, Versamune participates in the activation of NK cells, macrophages and dendritic cells that are important for general activation of the immune system and fight viral infections.
"In general, we can define this as a nanoparticle vaccine, which contains the S1 antigen, transmitted with a carrier. It is an immunizing that, when entering the cell, stimulates the entire immune system", summarizes Silva to the Journal of USP.
The investment brings together resources from the National Council for Scientific and Technological Development (CNPq), of Farmacore Biotecnologia Ltda. and the American PDS Biotechnology.
Here you can get closed captioning translated to English. Open the link, jump ahead to approximately 39 minutes into show, select CC, then click on Settings and change to Auto Translate and select your preferred language. Translation is a little hard to follow at times but you can get the jist of what is discussed. Sounds as if human trials will start at the end of May. I was hoping it would be sooner but that is only a couple of months from now.
Link
And another CNN Brazil story from Saturday, I like seeing Versamume in the heading. For anyone who understands Portuguese, the interview lasts 8 minutes, I wish I understood what CEO of Farmacore was saying.
Courtesy of Twitter.
Link to story
Versamune should be available in early 2022, ceo of Farmacore tells CNN
Helena Faccioli says the human testing phase should last between 9 and 12 months
Produced by ELIS Franco of CNN in São Paulo
March 27, 2021 at 3:18 PM
Last Updated Mar 27, 2021 3:27 PM
In an interview with CNN,the CEO of Farmacore Biotechnology, Helena Faccioli, explained the testing stages of Versamune, a vaccine against Covid-19 developed by the company in partnership with PDS Biotechnology and the Ribeirão Preto School of Medicine at the University of São Paulo (FMRP-USP).
According to Faccioli, the drug should be available for use in the population only in 2022. "Probably early next year," said the CEO of Farmacore.
"Our idea is that if the project is not interrupted, and everything runs normally, from the beginning of phase 1 to the completion in phase 3, it will be an interval of around 9 to 12 months so that we can submit the final data and request emergency use to Anvisa."
According to Faccioli, the first stage of the process involves testing on a smaller group of people: "We will evaluate 360 volunteers of different ages to see if the immunising will generate an immunogenicity, antibodies, and if it will not have adverse side effects."
The last phase of testing will have a larger number of individuals and evaluate the efficacy of the vaccine.
"It will be a multicenter study, which will involve around 20,000 people, in which we will identify whether it is effective and will protect against virus infection."
Additional CNN Brazil press:
[url]https://www.cnnbrasil.com.br/saude/2021/03/26/o-que-voce-precisa-saber-sobre-a-vacina-versamune-apoiada-pelo-governo-federal
[/url][tag]What you need to know about the Versamune vaccine, supported by the federal government[/tag]
What you need to know about the Versamune vaccine, supported by the federal government
Vaccine developed in Ribeirão Preto is the government's new bet against Covid-19
CNN's Gregory Prudenciano in Sao Paulo
March 26, 2021 at 6:37 p.m| Last Updated Mar 26, 2021 at 10:51 PM
The federal government's newest bet to combat the Covid-19 pandemic goes by the name versamune,a vaccine developed in Brazil and funded by the Ministry of Science, Technology and Innovations, which filed with Anvisa (National Health Surveillance Agency) the request for the first clinical trials in humans to be made.
Versamune is the result of a partnership between the Brazilian company Farmacore, based in Ribeirão Preto (SP), the American PDS Biotechnology and the Ribeirão Preto School of Medicine of the University of São Paulo (FMRP-USP).
How does it work?
In an interview with CNN,The CEO of Farmacore, Helena Faccioli, explained that, basically, Versamune has the Protein S-1, which prevents the virus from connecting to the cells of the body, avoiding the installation of the disease.
Even if the virus can bind to the cell, SARS-Cov-2 will be fought by T cells activated by a nano lipid particle also present in the vaccine, - roughly speaking, it is like a very small particle of fat.
Thus, the action of the immunizing is based on the interaction of these two compounds. If the work of the S-1 protein fails, the nano lipid particles will have "trained" t cells to combat the new coronavirus, which even helps that people who have contracted the virus once they do not go through a reinfection.
How many doses should be taken?
Two doses, with an interval of 21 days between them. To date, tests have been conducted in mice, and the immunological response has been very satisfactory: 98% of the animals were not infected by the virus. Of those who developed the disease, none died.
According to researcher Célio Lopes Silva, from FMRP-USP, Versamune will be more effective in protecting against the new coronavirus than vaccines currently being used because it is more efficient in killing infected cells.
How long should the tests last?
According to Helena Faccioli, clinical trials in humans are expected to last between six and nine months.
If Anvisa releases clinical trials, the companies will do the first two phases of testing on about 360 volunteers. The objective is to evaluate whether the vaccine generates the necessary antibodies and if there are no serious side effects.
Next comes phase three, which should have 20,000 to 30,000 volunteers and will serve to test whether the immunizer will actually offer the necessary protection on a day-to-day life.
"If it is a new vaccine, you have to obey the whole rite, do phase 1 and 2 studies, which are faster. In two months you can make them. But phase 3 trials, using a larger population from different states, take a while," explained Júlio Croda, an infectologist at the Oswaldo Cruz Foundation (Fiocruz).
When should the doses be ready?
The CEO of Farmacore said that the company is in negotiationwith a national pharmaceutical industry and that doses should be manufactured in paralalo with clinical trials. The expectation is that once the tests are completed, Versamune will already be able to meet between 30% and 40% of the Brazilian demand for vaccines.
She hopes that between January and February 2022 Anvisa is already analyzing a request for emergency use of the vaccine. If approved, distribution can be done immediately.
"As it is a simple and easy process, we should have an ability to meet at least 50% of the need for doses per year. We will work together with the Ministry of Science and Technology to supply the domestic market, producing between 400 and 500 million doses," faccioli said.
Logistics should be facilitated because the vaccine is made to be stored in common refrigerators, at temperatures ranging from 6ºC to 8ºC. In addition to supplying the domestic market, Farmacore wants Versamune to also serve other Latin American countries.
Who's paying?
"We received funding from the Ministry of Science and Technology to perform most of the clinical trials, but the initial investments were made by the company itself," says Helena Faccioli, who estimates spending R$ 20 million so far.
Phases 1 and 2 should demand an additional R$ 30 million, and the CEO assures that "the government has already signaled that it has the resource".
Phase 3, the most expensive, should demand an additional R$ 300 million. "You have to hire five more, six clinical centers in Brazil, each with seven to eight thousand volunteers," explains Faccioli, who already works in a "joint" with the portfolio so that these future expenses are also on behest the federal government.
"But the process still needs to go phase by phase so that we can also move forward in the next stages of resources," he said.
Company has experience in the veterinary market
In addition to Versamune, Farmacore also develops a tuberculosis vaccine, currently in testing period. However, the company has more experience of producing veterinary medicines, focusing on dogs, cows, salmon and even an oral vaccine for tilapia.
On the company's website, Imunivax is presented as the main product already developed. It is a veterinary drug aimed at the treatment of cancer, dermatitis, autoimmune diseases and infectious diseases, especially in dogs.
In the case of Imunivax, USP also appears as a partner of Farmacore, similar to what happens with Versamune. The university holds 30% of the patent ownership of the drug, while the company has 70%.
How many Brazilian vaccines do we have?
According to the Ministry of Health, 17 national studies of possible vaccines against Covid-19 from different origins are monitored. This week, two of these studies completed the phase of preclinical studies and requested permission to begin testing on humans.
One is The Versamune-CoV-2FC, from Farmacore, and the other is Butanvac, a Brazilian vaccine developed by the Butantan Institute in partnership with Dynavax and PATH.
Do you not see "March 2021 Presentation" in my post? Click that and it will bring you to PDS website.
I just finished listening to conference, very well done by Frank. I posted copies of slides on Twitter for those interested. This will not stay in single digits much longer imo. Here is link to current corporate presentation.
March 2021 Presentation
Is that wishful thinking or is it really happening?
You are correct BUT I hope they put off the offering until after ASCO and after the Covid trial has started. No need to do the offering in single digits as they have enough funds until some point next year. Also, they should do an ATM offering instead of giving the crooked investment bankers a chance to buy the offering at a huge discount. Sell into strength using an ATM of say $50 million.
So sorry for your loss. At the end of an episode of NCIS, they read this poem and I was so moved by it. Please take solace in its words and the beautiful memories of your wife.
Epitaph
By Merrit Malloy
When I die
Give what’s left of me away
To children
And old me that wait to die.
And if you need to cry,
Cry for your brother
Walking the street beside you.
And when you need me,
Put your arms
Around anyone
And give them
What you need to give to me.
I want to leave you something,
Something better
Than words
Or sounds.
Look for me
In the people I’ve known
Or loved,
And if you cannot give me away,
At least let me live on in your eyes
And not your mind.
You can love me most
By letting
Hands touch hands,
By letting bodies touch bodies,
And by letting go
Of children
That need to be free.
Love doesn’t die,
People do.
So, when all that’s left of me
Is love,
Give me away.
This could be why PDSB has been relatively strong the last couple of days, courtesy of Twitter. Once they get into the clinic, we should start to get more press.
Farmacore CNN article
Brazilian vaccine under study by Farmacore bets on long-term protection
CEO of Farmacore Biotechnology predicts that human testing will begin in the first half of 2021
CNN's Juliana Alves in São Paulo
March 7, 2021 at 2:01 PM
The National Health Surveillance Agency (Anvisa) received information from three brazilian covid-19 vaccine studies. One of these immunizations still in the pre-clinical phase is the Pharmacore Biotechnology, in partnership with the American PDS Biotechnology and the Faculty of Medicine of usp of Ribeirão Preto.
In an interview with CNN on Sunday (7), the CEO of Farmacore Biotechnology, Helena Faccioli, explains that the big difference of this immunizer, in the phase of animal testing, is the long duration of protective action.
"We have long-term animal tests that show that after a few months, if you expose the animals to coronavirus again, the body still produces an immune response. So it has a longer duration in people's bodies than other vaccines. It will protect for longer," he says.
Faccioli explains that all pre-clinical data have already been submitted to Anvisa. And that once they pass, the forecast is that this semester human trials will begin.
"We are already in negotiationwith the clinical centers and already have a selection of who will run the clinical trial for us," says the CEO. "Now it depends on our interaction with Anvisa to get started. But it will start this semester, of course," says the CEO.
According to Helena Faccioli, the final results of some tests on mice will be finalized in March. "To then submit the official and final package with these data and obtain the approval to perform the clinical trial in the volunteers," he adds.
So far, Anvisa has had access to the documentation of the pre-clinical stages and, according to the CEO, Farmacore has been holding some follow-up meetings with the agency's technical team.
Unlike immunizers already in use in Brazil, the Brazilian pharmacore vaccine focuses on the use of a recombinant protein derived from coronavirus.
"It is formed by a nano lipid particle and a recombinant protein that is S1. S1 is derived from coronavirus. A safe, easy to handle and easy to produce protein. It does not contain a piece of attenuated virus or virus or RNA or DNA. So it's simply a recombinant protein with a nano lipid particle," he explains.
Faccioli details that, since the initial project, the premise was to produce an immunizing that Brazil was technologically self-sufficient, precisely to avoid problems in the supply of supplies.
"We thought of technologies that were easy to produce, safe and that could be produced entirely in Brazil in the phase of mass vaccination. Some steps today are still performed by our American partner, but we are already in conversation and negotiation with a Brazilian pharmaceutical industry so that this process is here during phase 3, which is the longest."
It's available on their website. Very good presentation but very little mention of Covid treatment, seems to be downplaying it imo. I'm feeling he doesn't want to get caught up in hyping it. Spent far more time discussing the cancer potential which sounds very promising. Worth listening to for all investors and potential investors.
Feel very secure with my investment which is much higher than I ever thought. I think pdsb has the real potential to be one of my biggest gaining investments ever with the right news. With a market cap of around $100 million, it will only take 1 piece of the right news to drive this into the billion dollar++ market cap territory and could happen any day. GLTA