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brman- $14/sh p1 of spreadsheet with low multiples and patient size. Buyout multiples may vary of course.
You will see much higher traded companies with less (o8>
so the issue for CYDY is more it's unknown status.
We know it looks unreal from here, but I have also posted the references of usual multiples of sector and peers incl TaiMed.
Insanely cheap indeed, but that is how the market deals with certain stocks. Some are insanely overvalued and some the other way around. Therefor a market correction is expected the more credible company becomes, i.e. data data data.
chump- GvHD material FDA news before 5/9 ASM or its conclusion?
Well, I wouldn't say not this of course, but then FDA surely would get a medal for being fast (o8>
Either way, up she shall go.
One day, company will be known as Pro 140 already is.
Rwshay- IMHO next big news are the actual CD02 Combo Viral Load reduction numbers on 6/9 (to be published post ASM).
We know the PE has been reached, i.e. reduction more than 0.5log, but the whole coverage of Pro 140 performance and actual reduction between 0.5log and 1.8log(?).
GvHD just started its ph2 trial, therefor I believe this will be a catalyst after the whole CD02 Combo show.
misiu- I agree. Also we didn't get the 'Orphan Drug Designation' (ODD), indicating the bigger patient coverage.
Again, company cannot promote Pro 140 too loud due to FDA relations, others may step in soon post paper & ASM.
Evaluation wise we figures the upside is extreme even with low numbers from here and we also are able to compare with peers like IZ + THERF (aggregated of course).
Potential moves with rolling BLA are multiple as already discussed.
Roughly one month to go.
trding, misui - the low figure from March seems to match
the very floor expectation. This is still more than IZ gets
thanks to MDR 2. Also this is only US for 2019, we know that.
So even this low figure method will get higher over the years,
especially considering increased cases of MDR, company posted that in a tweet lately and Misui stated that as well.
The old higher figure (which presentation trding?) seems to
be more appropriate, but .. well, it might be too bullish.
Company shall not be too bullish and 'pumping' its stock,
while they are under FDA watch - they surely don't like that.
TL;DR: Even the low figure evaluation as posted is much higher than current stock price, much higher (o8>
So whatever it will be within the next 10 years, I bet it is right between those two min/max brackets 50k - 200k US patients.
+++
Regarding trading, d0lph et al., this could also consolidate down to 53c - 54c within the usual 3 days, could even flashing 51c intraday again. It doesn't matter.
I expect closing prices >= 53c, i.e. resistance became support.
In general this will recover for the big 5/9 ASM data poster and probably the related new paper.
Let others have some cheap shares as well, before the party really starts (o8>
d0lph- it's the missed train attitude as usual (o8>
TA wise 53c should hold, if reached bounce and will continue to walk up.
The 'but but there were no news' outcries and 'nothing soon' whining dismiss the facts of the value of this drug and of course the upcoming paper and ASM for CD02 PE achievement.
Misiu- Therefor March presentation covering MDR 2+3 is more on the bottom side of the potential market side. So our evaluation is quite a pessimistic lowest reasonable possible.
Good luck.
PS: I have to reduce my postings a bit, yesterday I exceeded my 15 free posts (o8>
law- thank you, but I don't like Seeking Alpha's TOS and paywall
Further I just compile information from this board, company and our little science community for our own good,
validating our investment thesis.
Since MCAP is so far under water compared with Pro 140 evaluation, this is truly a must have.
Our conclusion is known by now: Pro 140 is best in class CCR5-tropic HIV-1 treatment.
We may consider an alternative free access platform to expose these finding. However, unlike the company's stock, Pro 140 is very well known. Posting our summaries here should suffice.
Only 47 Calendar (32 workdays) days until 5/9 ASM presentation, inclusive.
misui- Right, I put 'biweekly' in Pro 140 general description, as well as in 2017-02 efficacy segment as shown in CROI.
For CD02 I will state weekly 350mg, shown next time. Correct.
Thank you.
misiu- thank you. So Doctors could mix & match the 'cocktail' for their patients. Also in a legally safe way if the label would state that a certain range of Pro 140 dosage has been tested and considered safe?
Let's say the ongoing CD03 high-dosage arm 700mg result is same safety data, a Doctor could then use a higher dosage for their CD02 Combo patients .. maybe?
I am sure that an ongoing post approval phase 4 trial can give more clarity in all these directions. I like the idea of individual dosage for the real world.
misui- question for the physician
The high-dosage arm exploration gives me this idea.
Can doctors adjust the dosage to match them individually?
We know there is no reported toxicity, but one might want only take the minimum dosage possible or a higher useful dosage in the long run. Whether this might be due to patient's CCR5 count or whatever influences the HIV-1 replication.
misui- in last 10-Q they mumble about the 50% higher dosage to increase the response rate for certain patients within the CD03 Mono trial.
I assume this is to test whether the rebounding patients are due to an patient's higher CCR5 receptor count.
I don't assume they will apply the higher dosage for all patients, hence they named it 'high-dosage arm'.
We remember, last year's CROI poster revealed these rebound patients and they were not due to a change in co-receptor tropism (HIV-1 mutation) nor due to any Pro 140 antibodies.
This is an excellent CD03 protocol adjustment IMO.
bucks- thanks to your question I updated myself on CD03 Mono.
Surely CD03 enrollment completion is a moving target and they like to boost it post CD02 enrollment or completion towards end of 2018, depending on appropriate funding.
That is IMO a great strategy.
The other dates in the calendar are emphasizing CD02 Combo,
which is the strongest driver for now, especially at a 84% discount for CD02 Combo value alone @ $3.28/sh lowest and most fully diluted evaluation.
Our fun question will always be: When will 'they' buyout the company. The longer they wait, the more expensive it gets for the suitor due to lower discounts towards finalizing the trials and applying for approval. The cheap early stage Pharmassets buyout was a good example, why most won't get bought out too early due to failure risk. But here, Pro 140 is at spitting distance to 100% risk-free.
Sorry for the bullish lines, but this is also on our mind (o8>
misiu- noted, thank. Next update will show (o8>
A very healthy community here, reviewing our summaries regardless whether in favor for Pro 140 or not.
Excellent and objective.
d0lph- yes, 20dma 53.38c (edited) and some party likes to keep it rising very slowly.
Last days we saw that intraday 10k sales to bring it down a little just to buy a few more up lower. That's OK.
Overall trend is up on daily, curving up:
- MACD histogram positive for one week now,
- MACD > Signal,
- RSI rising
- A/D flat, but CMF and MFL up.
55c support from pre February to be recovered.
Evaluation wise this is of course all a bad practical joke (o8>
Comparison HIV-1 Anti-infective antibodies (update)
See also HIV-1 Anti-infective antibodies review part-1.
Changes:
- CD03 Mono Updates
- Fostemsavir is in phase 3 as an MDR 3, not MDR 4
Competitors
- Pro 140 targeting host CCR5 receptor, MDR 2; Cytodyn, Combo Phase 3 until September 2018: R > 0.5log10 up to 1.8log10
- Ibalizumab (IZ) targeting host CD4 receptor, MDR 3; TaiMed+THERF approved 2016-2018, 46% VL reduction, AEs + SAEs
- Fostemsavir targeting HIV-1 gp120 protein , MDR 3; ViiV Healthcare + GSK, phase 3 until 2020: 18% AEs + SAEs, R 0.62 log10 c/mL
MDR = multi-drug resistant, lower is better due to earlier treatment and more patients
Pro 140, owner Cytodyn
- Targeting host CCR5 receptor, blocking CCR5-tropic HIV-1 from entering
- MDR 2. Spec: May apply for MDR 0 post mono trial
- Weekly or biweekly subcutaneous self-administered PRO 140 injection
- Viral Supression in short range study of 0.5log10 up to 1.8log10, undetectable long term
- Undisputed in scientific community at least since 2000, covered by peer reviewed papers and cited in reviews
- Safety profile is extraordinary, especially since Pro 140 does not impact CCR5 host receptor normal operations
- No detected Pro 140 antibodies in any patient.
- Safety Profile re 2017-02 Combo n=16
-- No drug related SAEs
-- No discontinuation due to AEs, 25-50% drug related if at all
-- No pattern of toxicity
-- No dose-limiting toxicity in studies
-- Mono trial will clarify safety profile in more details
- Efficacy re 2017-02 Combo n=16
-- R 0.9log10 @ 162mg weekly
-- R 1.2log10 @ 324mg biweekly
-- R 1.5log10 @ 324mg weekly
-- Max impact after one week post injection
-- No PRO 140 antibodies detected in any subject!
-- No change in co-receptor tropism at virologic rebound (5/16)
- Efficacy re 2018-02 CD02 Pivotal Combo n=52
-- PE CD02 Combo: R > 0.5log10 @ 350mg, 1 week after 1 subcutaneous injection of PRO 140
-- PE reached in CD02 Combo Part-1
-- Details via poster on 6/9 @ ASM Microbe 2018
- CD02 Pivotal Combo Phase 3, 52 patients for 25 weeks, up until September 2018
-- Part-1 Efficacy R > 0.5log10 1 week after 1 350mg injection, reached
-- Part-2 OBT phase fro 24 weeks
-- Safety data of CD03 Mono to support rolling BLA submission, orig from 100pt.
-- 6/9/18 CD02 Pivotal Phase 3 Endpoint Achieved (ASM Microbe late breaker)
-- 3Q18: BLA Submission for CD02 Combo (rolling BLA)
-- 2019: CD02 HIV Combination Therapy Approval w/ BTD
-- ClinicalTrials.gov Identifier: NCT02483078
- CD03 Mono Phase 3, 300 patients for 48 weeks
-- Enrollment started in December 2016 to complete 4Q18.
-- Completion date around 2Q19 - 3Q19, depending on enrollment.
-- Provides safety data for CD02 Pivotal Combo Phase 3
-- Primary Endpoint: Responder rate above 70%
-- Secondary Endpoint: Non-responders can resume orig HAART therapy w/o resistance
-- Currently exploring a high-dose arm, with a 50% increase is dosage to evaluate
.. an increased response rate among certain patients
-- Expects to increase the number of sites in order to accelerate enrollment following
the completion of enrollment of the pivotal combination therapy trial & availability of additional capital.
-- Safety results supporting CD02 Combo BLA submission, orig from 100 patients
-- 4Q18: CD03 Phase 2b/3 Mono Investigative Trial Readout (probably later, CD03 completion around 2Q19)
-- ClinicalTrials.gov Identifier: NCT02859961
- CD01 Extension Study
-- 6/9 patients completed over 2.5 years on PRO 140 monotherapy, since around 2015.01
- Mono Phase 2 Study, 44 patients for ~5 weeks, successfully completed
- Paper https://www.ncbi.nlm.nih.gov/pubmed/20377413?dopt=Abstract
-- ClinicalTrials.gov Identifier: NCT00642707
Ibalizumab (IZ) Comparison Details, owner TaiMed
- Targeting host CD4 receptor, blocking HIV-1 from entering
- MDR 3
- TaiMed MCAP $2.2B
- US + Canada retail sales partner Theratechnologies MCAP $697.29M
-- THERF got a 5-10% royalty deal w/ TaiMed, but license 'only' for US and Canada
-- THERF to pay $10 million once annual sales of $200 million are reached in the US.
-- That goes up to a $100 million if they can break the $1 billion mark.
- Total $2.9B MCAP
- TaiMed MCAP rose to ~$1.6B shortly after filing of their BLA
- TaiMed was approved by the FDA in March, 2018, their market cap is USD$2.2B now.
- IZ trial had only 30 patients in their ph3 and no MONO objective, only COMBO
- IZ 43% achieved HIV RNA suppression after 24 weeks of Trogarzo.
- IZ common adverse events: diarrhea, dizziness, nausea and rash.
- IZ severe adverse events: rash and immune reconstitution syndrome,
..a condition in some HIV patients where the immune system recovers but then responds
..to a previously acquired opportunistic infection with an overwhelming immune (inflammatory) response.
- IZ is currently approved and roughly equivalent in terms of market size as PRO-140,
but actually should have smaller market size see below
IZ overall market size is smaller to Pro 140 due to
- COMBO only, Pro-140 applies for Mono as well and GvHD
- 3 Drug MDR, instead of 2 Drug MDR for Pro-140. Earlier treatment & more patients for Pro 140.
- IM IV not approved yet, also not “self-administration” route like SC injection of Pro-140,
which is a significant financial savings and care-plan/logistical advantage
- 43% Viral Suppression instead of nearly 99% w/ Pro-140
- Having AEs and even SAEs, Pro-140 has only little AEs if drug related at all
Fostemsavir Comparison, owner ViiV/GSK
- Targeting HIV-1 gp120 protein, blocking HIV-1 from entering
- Fostemsavir look very interesting , but phase 3 for mostly very sick MDR 3 patients only.
- After 24 weeks 54% of patients with viral load below 40copies/mill
- Information about side effect is still not complete.
371 total patients during study with Fostemsavir.
- 17 deaths during study ( 5% ) - due to progression of HIV.
- 91% of patients developed at least one side effect.
- 18% of patients developed mild , moderate-severe side effects.
- 9 patients ( about 2.5% ) developed severe side effects.
- 21 patients ( about 6% ) had side effects that caused them to leave the study.
Fostemsavir might be more a competition to Ibalizumab for now, but not really to Pro 140
When using Pro 140 most of CCR5 patients will not regress to MDR 3 most likely.
Most likely: Fostemsavir could be used for very sick MDR 3 patience for non-CCR5 HIV-1
bucks- re CD03 Mono - Catalyst Calendar
CD03 Mono completed Primary?
I doubt that, NCT02859961 website is not always up to date.
However, in last 10-Q they claimed 300 pt CD03 Mono enrollment to be completed in 4Q18.
I will update the overview again (o8>
Catalyst Calendar from March 2018 Presentation
- 2Q18: Publication of CD03 Mono (Phase 2b)
- 2Q18: Publication Studies – CD02 Combo Primary Endpoint Study
- 6/9/18 CD02 Pivotal Phase 3 Endpoint Achieved (ASM Microbe late breaker)
- 3Q18: BLA Submission for CD02 Combo
- 4Q18: CD03 Phase 2b/3 Mono Investigative Trial Readout (probably later, CD03 completion around 2Q19)
- 2018: HIV Breakthrough Therapy Designation (BTD)
- 2019: HIV Combination Therapy Approval w/ BTD
Note the CD02 Combo timing or publications, ASM, BLA and completion!
misiu- I will correct it with next update, thank you!
Compilation Update
2018-02-20 - Pro 140 Phase 2b/3 Pivotal PE Achieved
2018-04-19 - Evaluation Update
Pro 140 Related Publications, Opinion
Comparison HIV-1 Anti-infective antibodies,
- see also HIV-1 Anti-infective antibodies review part-1,
-- Fostemsavir part-2,
-- Maravaroc part-3,
- see also TaiMed/Theratechnologies Original Comparison by z_smith, part-1, part-2
-- Theratechnologies (THERF) Details
-- Historical Pharmasset Cheap Buyout in Early Stage
CEO Letter to Investor 2018-04-10
Pro 140 Related Publications (update)
+++
Opinion
Science is genuine, Pro 140 found before 1999 and is well covered in the scientific community via peer reviewed papers - undisputed.
Safety profile is extraordinary, especially since Pro 140 does not impact CCR5 host receptor normal operations.
2017's CROI poster's data also demonstrated how well Pro 140 does scale with dosage and frequency of administration.
The Viral Load suppression curve matches its method of action.
No detected Pro 140 antibodies in any patient.
Efficacy on CCR5-tropic HIV-1 has been proven since 2010 and we are looking forward to the latest trial data,
a paper before June's ASM and/or the poster at June's ASM the latest.
+++
2018.03 Engineering therapeutic antibodies to combat infectious diseases
https://www.sciencedirect.com/science/article/pii/S2211339817300497
2017.09 New Drugs in the Pipeline for the Treatment of HIV: a Review
https://link.springer.com/article/10.1007%2Fs11908-017-0601-x
2017.06 ASM Microbe '17 Poster: Interim Results in a Phase 2b/3 Pivotal Study of PRO 140
in Treatment Experienced HIV-1 Patients with Multiple ARV Class Resistance
https://content.equisolve.net/cytodyn/media/f800c6057fab55bfa6e3e5fdca0958b2.pdf
2017.02 CROI '17 Poster: PRO 140 Single-Agent Maintenance Therapy for HIV-1 Infection: A 2-Year Update
https://content.equisolve.net/cytodyn/media/506e06db35c45e222df77b15e7b5fc98.pdf
2014.02 CCR5 Plays Important Roles in Hepatitis B Infection
http://online.liebertpub.com/doi/abs/10.1089/vim.2013.0067#/doi/abs/10.1089/vim.2013.0067
2011.03 The Monoclonal CCR5 Antibody PRO-140: The Promise of Once-Weekly HIV Therapy
https://link.springer.com/article/10.1007%2Fs11904-010-0068-y
2010.10 Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
http://aac.asm.org/content/54/10/4137.full
2010.05 Anti-HIV-1 Activity of Weekly or Biweekly Treatment with Subcutaneous PRO 140, a CCR5 Monoclonal Antibody
https://academic.oup.com/jid/article/201/10/1481/992206 (free)
https://www.ncbi.nlm.nih.gov/pubmed/20377413?dopt=Abstract
2010.03 PRO 140 (a CCR5 monoclonal antibody) for treatment in people with HIV infection
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD008439/full
2010.01 Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
http://aac.asm.org/content/54/10/4137.short
2009.10 Review Pharmacotherapy of HIV-1 Infection: Focus on CCR5 Antagonist Maraviroc
http://insights.sagepub.com/redirect_file.php?fileId=2397&filename=1701-CMT-Pharmacotherapy-of-HIV-1-Infection:-Focus-on-CCR5-Antagonist-Maraviroc.pdf&fileType=pdf
2008.11 Antiviral Activity of Single-Dose PRO 140, a CCR5 Monoclonal Antibody, in HIV-Infected Adults
https://academic.oup.com/jid/article/198/9/1345/834086 (free)
2006.06 Potent Antiviral Synergy between Monoclonal Antibody and Small-Molecule CCR5 Inhibitors of Human Immunodeficiency Virus Type 1
http://aac.asm.org/content/50/10/3289.abstract?sid=f07d13da-4174-4f2e-b7bc-8d203d0b808d
2001.01 Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140
http://jvi.asm.org/content/75/2/579.short
2000.10 Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140
http://jvi.asm.org/content/75/2/579.abstract?site=JVirol&utm_source=TrendMDJVirol&utm_medium=TrendMDJVirol&utm_campaign=trendmdalljournals_0
Comparison HIV-1 Anti-infective antibodies (update)
Thank you all in board here for your input.
See also HIV-1 Anti-infective antibodies review part-1
Competitors
- Pro 140 targeting host CCR5 receptor, MDR 2; Cytodyn, Combo Phase 3 until September 2018: R > 0.5log10 up to 1.8log10
- Ibalizumab (IZ) targeting host CD4 receptor, MDR 3; TaiMed+THERF approved 2016-2018, 46% VL reduction, AEs + SAEs
- Fostemsavir targeting HIV-1 gp120 protein , MDR 4; ViiV Healthcare + GSK, phase 3 until 2020: 18% AEs + SAEs, R 0.62 log10 c/mL
MDR = multi-drug resistant, lower is better due to earlier treatment and more patients
Pro 140, owner Cytodyn
- Targeting host CCR5 receptor, blocking CCR5-tropic HIV-1 from entering
- MDR 2. Spec: May apply for MDR 0 post mono trial
- Weekly or biweekly subcutaneous self-administered PRO 140 injection
- Viral Supression in short range study of 0.5log10 up to 1.8log10, undetectable long term
- Undisputed in scientific community at least since 2000, covered by peer reviewed papers and cited in reviews
- Safety profile is extraordinary, especially since Pro 140 does not impact CCR5 host receptor normal operations
- Safety Profile re 2017-02 Combo n=16
-- No drug related SAEs
-- No discontinuation due to AEs, 25-50% drug related if at all
-- No pattern of toxicity
-- No dose-limiting toxicity in studies
-- Mono trial will clarify safety profile in more details
- Efficacy re 2017-02 Combo n=16
-- R 0.9log10 @ 162mg weekly
-- R 1.2log10 @ 324mg biweekly
-- R 1.5log10 @ 324mg weekly
-- Max impact after one week post injection
-- No PRO 140 antibodies detected in any subject!
-- No change in co-receptor tropism at virologic rebound (5/16)
- Efficacy re 2018-02 CD02 Pivotal Combo n=52
-- PE CD02 Combo: R > 0.5log10 @ 350mg, 1 week after 1 subcutaneous injection of PRO 140
-- PE reached in CD02 Combo Part-1
-- Details via poster on 6/9 @ ASM Microbe 2018
- CD02 Pivotal Combo Phase 3, 52 patients for 25 weeks, up until September 2018
-- Part-1 Efficacy R > 0.5log10 1 week after 1 350mg injection, reached
-- Part-2 OBT phase fro 24 weeks
-- ClinicalTrials.gov Identifier: NCT02483078
- CD03 Mono Phase 3, 300 patients for 48 weeks
-- Full enrollment 300 by 4Q17
-- Provides safety data for CD02 Pivotal Combo Phase 3
-- ClinicalTrials.gov Identifier: NCT02859961
- CD01 Extension Study
-- 8/9 patients completed over 2.5 years on PRO 140 monotherapy, since around 2015.01
- Mono Phase 2 Study, 44 patients for ~5 weeks, successfully completed
- Paper https://www.ncbi.nlm.nih.gov/pubmed/20377413?dopt=Abstract
-- ClinicalTrials.gov Identifier: NCT00642707
Ibalizumab (IZ) Comparison Details, owner TaiMed
- Targeting host CD4 receptor, blocking HIV-1 from entering
- MDR 3
- TaiMed MCAP $2.2B
- US + Canada retail sales partner Theratechnologies MCAP $697.29M
-- THERF got a 5-10% royalty deal w/ TaiMed, but license 'only' for US and Canada
-- THERF to pay $10 million once annual sales of $200 million are reached in the US.
-- That goes up to a $100 million if they can break the $1 billion mark.
- Total $2.9B MCAP
- TaiMed MCAP rose to ~$1.6B shortly after filing of their BLA
- TaiMed was approved by the FDA in March, 2018, their market cap is USD$2.2B now.
- IZ trial had only 30 patients in their ph3 and no MONO objective, only COMBO
- IZ 43% achieved HIV RNA suppression after 24 weeks of Trogarzo.
- IZ common adverse events: diarrhea, dizziness, nausea and rash.
- IZ severe adverse events: rash and immune reconstitution syndrome,
..a condition in some HIV patients where the immune system recovers but then responds
..to a previously acquired opportunistic infection with an overwhelming immune (inflammatory) response.
- IZ is currently approved and roughly equivalent in terms of market size as PRO-140,
but actually should have smaller market size see below
IZ overall market size is smaller to Pro 140 due to
- COMBO only, Pro-140 applies for Mono as well and GvHD
- 3 Drug MDR, instead of 2 Drug MDR for Pro-140. Earlier treatment & more patients for Pro 140.
- IM IV not approved yet, also not “self-administration” route like SC injection of Pro-140,
which is a significant financial savings and care-plan/logistical advantage
- 43% Viral Suppression instead of nearly 99% w/ Pro-140
- Having AEs and even SAEs, Pro-140 has only little AEs if drug related at all
Fostemsavir Comparison, owner ViiV/GSK
- Targeting HIV-1 gp120 protein, blocking HIV-1 from entering
- Fostemsavir look very interesting , but phase 3 for mostly very sick MDR 4 patients only.
- After 24 weeks 54% of patients with viral load below 40copies/mill
- Information about side effect is still not complete.
371 total patients during study with Fostemsavir.
- 17 deaths during study ( 5% ) - due to progression of HIV.
- 18% of patients developed mild , moderate-severe side effects.
- 9 patients ( about 2.5% ) developed severe side effects.
- 21 patients ( about 6% ) had side effects that caused them to leave the study.
- 91% of patients developed at least one side effect.
Fostemsavir might be more a competition to Ibalizumab for now, but not really to Pro 140
When using Pro 140 most of CCR5 patients will not regress to MDR 3 or 4 most likely.
Most likely: Fostemsavir could be used for very sick MDR 4 patience for non-CCR5 HIV-1
misiu- excellent Fostemsavir summary
My Compilation so far
2018-02-20 - Pro 140 Phase 2b/3 Pivotal PE Achieved
2018-04-19 - Evaluation Update
- TaiMed/Theratechnologies Original Comparison by z_smith, part-1, part-2
- Theratechnologies (THERF) Details
- Historical Pharmasset Cheap Buyout in Early Stage
Pro 140 Related Publications
HIV-1 Anti-infective antibodies review part-1,
- Fostemsavir part-2,
- Maravaroc part-3,
- Opinion part-4
CEO Letter to Investor 2018-04-10
re Pro 140 Review (WIP), our opinion/findings
Science is genuine, Pro 140 found before 1999 and is well covered in the scientific community via peer reviewed papers - undisputed.
Safety profile is extraordinary, especially since Pro 140 does not impact CCR5 host receptor normal cause of operations.
2017's CROI poster's data also demonstrated how well Pro 140 does scale with dosage and frequency of administration. The Viral Load suppression curve matches its method of action.
Efficacy on CCR5-tropic HIV-1 has been proven since 2010 and we are looking forward to the latest trial data, a paper before June's ASM and/or the poster at June's ASM the latest.
+++
And now, we can simply wait until market catches up with the science and commercial application.
Fostemsavir Phase 3 to be completed in 2020, as noted in excerpt and see https://www.viivhealthcare.com/media/press-releases/2017/october/viiv-healthcare-announces-positive-phase-3-results-from-the-brighte-study-of-fostemsavir-in-heavily-treatment-experienced-patients-with-hiv.aspx
Fostemsavir so far has also shown AEs and SAEs, which company has been blamed on the patients sever health situation. Well ..
The Pro 140 paragraph in the 2017 review uses old data using the phase 2a infusion route and SC route (edited).
Need to find a more up-to-date review of data, so far the company's posters seem to be the best choice.
HIV-1 Anti-infective antibodies review
Work in Progress (WIP)
So far then, competitor field is:
- Ibalizumab (IZ) targeting host CD4 receptor, TaiMed+THERF approved 2016-2018, 46% VL reduction, AEs + SAEs
- Fostemsavir targeting HIV-1 gp120 protein , ViiV Healthcare + GSK, phase 3 success: 0.79 log10 c/mL vs 0.17 log10 c/mL; p<0.0001, 18% AEs
- Pro 140 targeting host CCR5 receptor, Cytodyn, phase 3 until August 2018: > 0.5log10 p<0.01 up to >=1.8log10
Would be great if we can detail the overall competitor field.
Thanks to 01, Nuptse & Zhang
+++
"Engineering therapeutic antibodies to combat infectious diseases", Ellen K Wagner and Jennifer A Maynard, March 2018
+++
"New Drugs in the Pipeline for the Treatment of HIV: a Review",
Sep 2017
misiu- thank you.
Hope your son is well and hasn't been infected.
I understand this was a precaution measure preventing or limiting initial exposure.
We have not claimed that Pro 140 is a lie, of course not,
'just' want to back check from a research perspective.
So far - all does look very credible - from research.
We just wanted to walk the possible negative checklist here, that is all. Always triple check everything what could possibly go wrong.
Yes, the AE anti-thesis is indeed ridiculous (o8>
Therefor, we simply continue to DD, hold & smile.
bucks- from an insider or believer position yes, you are right.
But compare this with an outsider first reader about Pro 140 and compare it to the standard of care. It is a very strong claim.
Good for us, soon to be properly shown as validated.
Science Credibility Rules Indeed
Excuse my long post, I wanted to elaborate about our little group's last conversation.
We were not able to gather any in new findings, but we would love to read other professional viewpoints - Misiu's for example.
It all seems to boil down to the one question: Is Pro 140 for Real?
I debated the whole situation with our chem/bio Phd focusing on credibility of the science over the weekend.
She asked:
- Were peer reviewed papers published before finishing phase 2? Yes.
- How and why did they moved to the new Combo trial?
The Combo trial seems to have created the fast make it or break it event, validation of all claims.
The PE has been chosen quite dramatically, especially if comparing to existing drugs.
She was quite impressed that company even agreed upon the one week threshold of just one injection for the 0.5log or 68% viral load reduction. This was a do or die event for the company.
Desperate and highly risky.
We know why they did it this way.
Limited funds demanded such a short cut trial to prove the high efficacy claims of Pro 140.
Stock regained value and plunged back to TO offering price.
Next discussion point was about chances that company is simply lying about claims and results, is it even possible?
Pro 140 is working based on peer reviewed papers, previously proven by many (open) trials.
Data has been continuously presented via non peer reviewed posters. Next will come on in June for PE.
She asked: 'Did anything go wrong? How many patients died?'
None of such events has been posted.
Following sector typical impact factor pattern, she says, the more credible the poster venue is and the higher the impact factor of the journals, the higher the credibility of the drug.
Misiu, are you satisfied with the published Pro 140 papers so far?
She believes that the researcher would like to publish a paper on the achieved PE before publishing the poster in June. They can't publish their paper about PE data after publishing the data in the poster due to required novelty. Such paper is not really required, method has been published with given data, but because that's what they do .. papers papers papers (o8>
As of now, claimed outcome is sort of outrageously positive, especially given what kind of company this is - we know that.
IZ has 'only' some 48% overall proven viral load reduction, where Pro 140 claims to have achieved 68% within one week and eventually will leave VL undetectable, i.e. 99%. This is almost too good to be true.
This marks a huge gap between the claim and the current standard of care. A dramatic breakthrough.
However, if company is able to prove said claims, i.e. showing controlled data points and outcome of this trial, it is done. Certainly, the Martin Sheen stunt didn't really help giving this company professional credibility.
As shown in our evaluation, the dilution has little impact on the resulting overall value, even though the TO or raise at 50c looked ugly and was clumsy at best.
As many put it here on the board: Forget the financials - the drug is everything. We agree.
Until today, we haven't seen any credible attack on the science yet, just the outcries about the clumsy financing.
I asked my friend about the one anti-thesis as posted here frequently, whether little or no toxicity or adverse effects (AEs) contradict the drugs efficacy. She rejected this notion with a smile, since AEs are not necessarily the result of the desired method of operation, but often caused by additional undesired side or adverse effects. Pro 140's working method is not based on harming healthy cells, i.e. toxicity. Its ability to block the HIV-1 CCR5 docking port without interrupting otherwise healthy and desired functions seems to have been proven with achieved PE plus old and new upcoming safety data.
Therefor AEs are not at all a required implication for any drug's potency. I have read a similar statement from Misiu here.
saltz- don't underestimate 6/9 PE data poster as the very next catalyst.
While I searched the net, PE achievement has had very little coverage so far, as if it doesn't exit yet.
Even the Pro 140 Wikipedia entry just recently added the event
and professional coverage seems to ignore its success.
Drug and company is under-reported.
However, make no mistake, reaching PE in the ph2b/3 pivotal trial is the most important event for Pro 140's very existent in our eyes, being backed up by credible data. The latter will be confirmed at ASM and via BLA acceptance the very latest.
It elevates drug and company from the foggy area of a thinly traded company under the radar begging for money, which pushes forward a previous neglected drug.
Criticism I have read so far simply focuses on the harsh capital raises, some even were yelling fraudulent behavior.
Such ridiculous blinded viewpoints shall be dismissed, that's where shown evaluation shall step in. The posted list of scientific publications already illustrate the underlying awareness of Pro 140 and its new reality.
Soon everybody may talk more about the drug and its proven potential than the financial hardship company endured to reach the point of success.
Company & supportive shareholders shall be very proud of themselves having succeeded this marathon.
The end of Pro 140 speculation, the beginning of Pro 140 reality.
d0lph- thank you, still we have that 'trading overhead'
of roughly 131M Options & Warrants at $0.80 average.
My replies for extreme doomsday melody is emphasizing the company's underlying
value. June's Combo ASM and especially August's complete Combo readout and subsequent BLA filing will be an extreme liquidity event, as it's being defined with high volume and demand.
Investors trying to partake in the new value but trying to safe investment time will pay a higher price to enter of course. Some others not realizing the potential may sell for their low price target. Shorts usually have exited before.
We discussed this using TaiMed and such positive reality events correct the MCAP always.
Meaning June - September is the period in time where the commercial value of Combo will be added to MCAP with a much lower discount.
That being said, we also know that February's PE PR - while moving us up, was overshadowed by those clumsy 50c Warrants TO,
which company didn't recall in time. Therefor they took their profits as well as many Series-B convertibles, probably.
Add the RS scare and what-not bashing, we ended up at the predicted SP of 50c, which I called back then because of said mechanisms.
This is normal market behavior for a short period of time.
In June Company goes on record publishing the data for the PE,
meaning it will receive broad coverage and gets referenced almost everywhere in the media and especially in other scientific publications later on.
The success probability of analysts will be increased materially and therefor their discount reduced.
I don't know how long the BLA filing will take though.
So back to trading reality, we still need to go through the 131M Options and Warrants @ 80c, assuming half of them would like to sell within $1 - $1.20, see below.
Usually, to my experience, after a material event such as PE data and/or BLA acceptance and/or FDA approval, even Warrant holder at 80c won't dump below value. See TaiMed, THERF or the many other biotech companies. All of them have such Warrant overhead from previous offerings.
Knowing this, also allows stock to walk back up to this 80c + 10% without the fear of hitting a big wall earlier. At least this range here is very good to buy, as long its available IMHO.
Hopefully my view is quite balanced. Nothing can be predicted perfectly of course and the market always reacts a bit differently earlier, or later.
Gladly PE has reached, believing the PR states the truth and we consider this now an almost risk-off investment.
Good luck.
(From April 10-Q, Notes Table, Stock Options and Warrants)
martygx- thank you, not a bad viewpoint.
You are giving us a healthy critical opinion
and I thank you for that, since one shall always
review ones analysis and standpoint IMHO.
Yes, the outcome has been PR'ed, however underlying data has not been published as of today. The technical difference is that the PR is hearsay, but data at ASM are reviewed facts.
However, the poster has been accepted already.
So that is about Combo and market is playing its games. OK.
Final result of August BLA should be comforted with a SP above $1.50.
In case of Mono, we may say that a change of protocol causing increased costs will be handled after Combo outcome in August at a much favorable financing model.
martygx- which brings us to
accepted 6/9 ASM Microbe Poster Session, where company will disclose the underlying data of having reached Primary Endpoint and therefor making this event public, published and credible.
2018-06-09 11am - 1pm: ASM Microbe 2018 Poster Session
https://www.cytodyn.com/media/press-releases/detail/274/cytodyn-to-present-primary-efficacy-endpoint-results-from
- announces that an abstract with primary efficacy results from its PRO 140 pivotal combination therapy trial in treatment-experienced
HIV patients has been accepted for presentation at a late-breaking session at ASM Microbe 2018.
The conference is being held June 7-11, 2018 at the Georgia World Congress Center in Atlanta.
http://www.abstractsonline.com/pp8/#!/4623/presentation/15313
- AAR LB15 / SATURDAY - AAR LB15 - Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients
martygx- hence I posted list of publications post #21863
d0lph- link is below daily short chart
d0lph- thank you. I use the 8dema, similar result
Price and 8dema converging while MACD is positive.
The past golden cross with high volume is supportive.
Yes, 'just' TA.
Very interesting is the high daily short increase,
as if we are just buying their borrowed shares - lovely.
via http://volumebot.com/?s=cydy
Could be also meaningless, if those were just borrowed to satisfy retail brokerage while trading.
Bottom line IMHO .. we are there (o8>
Pro 140 Related Publications, anyone missing?
2018.03 Engineering therapeutic antibodies to combat infectious diseases
https://www.sciencedirect.com/science/article/pii/S2211339817300497
2017.09 New Drugs in the Pipeline for the Treatment of HIV: a Review
https://link.springer.com/article/10.1007%2Fs11908-017-0601-x
2017.06 ASM Microbe '17 Poster: Interim Results in a Phase 2b/3 Pivotal Study of PRO 140
in Treatment Experienced HIV-1 Patients with Multiple ARV Class Resistance
https://content.equisolve.net/cytodyn/media/f800c6057fab55bfa6e3e5fdca0958b2.pdf
2017.02 CROI '17 Poster: PRO 140 Single-Agent Maintenance Therapy for HIV-1 Infection: A 2-Year Update
https://content.equisolve.net/cytodyn/media/506e06db35c45e222df77b15e7b5fc98.pdf
2014.02 CCR5 Plays Important Roles in Hepatitis B Infection
http://online.liebertpub.com/doi/abs/10.1089/vim.2013.0067#/doi/abs/10.1089/vim.2013.0067
2010.10 Phase 2a Study of the CCR5 Monoclonal Antibody PRO 140 Administered Intravenously to HIV-Infected Adults
http://aac.asm.org/content/54/10/4137.full
2010.03 PRO 140 (a CCR5 monoclonal antibody) for treatment in people with HIV infection
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD008439/full
2009.10 Review Pharmacotherapy of HIV-1 Infection: Focus on CCR5 Antagonist Maraviroc
http://insights.sagepub.com/redirect_file.php?fileId=2397&filename=1701-CMT-Pharmacotherapy-of-HIV-1-Infection:-Focus-on-CCR5-Antagonist-Maraviroc.pdf&fileType=pdf
2006.06 Potent Antiviral Synergy between Monoclonal Antibody and Small-Molecule CCR5 Inhibitors of Human Immunodeficiency Virus Type 1
http://aac.asm.org/content/50/10/3289.abstract?sid=f07d13da-4174-4f2e-b7bc-8d203d0b808d
2000.10 Potent, Broad-Spectrum Inhibition of Human Immunodeficiency Virus Type 1 by the CCR5 Monoclonal Antibody PRO 140
http://jvi.asm.org/content/75/2/579.abstract?site=JVirol&utm_source=TrendMDJVirol&utm_medium=TrendMDJVirol&utm_campaign=trendmdalljournals_0
trding- well said. Little recap..
It crossed my mind as well, company didn't overstate market size, but probably made an understatement. Why? Possibly due to same reasons showing the evaluation makes people laugh compared to current traded value?
The combo filter criteria got indeed lightened up lately and voila, enrollment kicks in.
A little Combo Primary Endpoint Recap, this awesomeness seems to have been all forgotten. Good morning.
2018-02-20 PE Combo Reached p<0.01, HIV-1 RNA Viral Load Reduction > 0.5log (or 68%) within One Week & One Injection
Official PR https://globenewswire.com/news-release/2018/02/20/1361653/0/en/CytoDyn-Reports-Primary-Endpoint-Achieved-in-PRO-140-Pivotal-Combination-Therapy-Trial-in-HIV-Infection.html
-- Enrolled patients all had plasma HIV-1 RNA ≥400 copies/mL and documented detectable viral load within three months prior to the screening visit.
-- In the one-week, randomized, double-blind, placebo-controlled portion of the trial,
all trial patients received their existing ART therapy, with one-half of the enrolled patients administered a 350mg subcutaneous injection of PRO 140
-- The trial’s primary endpoint was the proportion of participants with greater than 0.5log reduction in HIV-1 RNA viral load from baseline at the end of the one-week treatment period
-- At one week, patients in the PRO 140 arm showed a statistically significant reduction in HIV-1 RNA viral load of greater than 0.5log from baseline versus patients in the placebo arm, (p<0.01)
-- Following this one-week period, all patients continue in the trial for an additional 24 weeks with PRO 140 weekly subcutaneous injections and optimized ART.
-- It is truly exciting that PRO 140 surpassed the one-week viral load reduction endpoint in what is certainly our most significant clinical trial result to date for this therapeutic candidate,
POZ https://www.poz.com/article/injectable-pro-140-hiv-treatment-hits-research-milestone
-- a single injection reduced study participants’ viral load by half a power of 10 (68 percent) - Note, that is 0.5log reduction
-- After one week, those who received PRO 140, received a greater than half a power of 10 reduction in their viral load compared with those who received the placebo.
Finalizing Trial:
-- Trial continues for 24 weeks, 6 month
-- 2018-08-20 End
-- Then BLA
2018-06-09 11am - 1pm: ASM Microbe 2018 Poster Session
https://www.cytodyn.com/media/press-releases/detail/274/cytodyn-to-present-primary-efficacy-endpoint-results-from
-- announces that an abstract with primary efficacy results from its PRO 140 pivotal combination therapy trial in treatment-experienced
HIV patients has been accepted for presentation at a late-breaking session at ASM Microbe 2018.
The conference is being held June 7-11, 2018 at the Georgia World Congress Center in Atlanta.
http://www.abstractsonline.com/pp8/#!/4623/presentation/15313
-- AAR LB15 / SATURDAY - AAR LB15 - Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients
bucks- $1.6B annual revs -> $7B mcap-2 max after BLA
That's P/S 4.38, not too high. TaiMed is currently traded much much higher.
Sure, one would combine value of TaiMed + THERF for a proper
comparison, thank you z_smith!
As repeated alot today, these are usual analyst ratings multiples.
For the sake of peace, you may wait for 50% of this $7B mcap-2, one step before max'ing out profits :)
Seriously, this value could hit if company just continues and the drugs are successful. At least Combo is very soon due to be successful, leaving us with a minimum of $1.6B mcap-2 while neglecting the other drugs.
Those will be added to the mcap as we go, showing progress.
Good luck to us.
misiu- thank you
yes, THERF has only a limited license in Canada + US
for this Combo. And all other limitations (differences)
as shown for TaiMed IZ do apply here as well, naturally.
CYDY owns Pro-140 with just a 12.5% royalty, for any coming drug.
Good stuff, so our MCAP boost on BLA should be higher than THERF, proving just again that Pro-140 does work.
-misiu THERF, excellent. Now we need to check how high their royalty is towards owner TaiMed?
Their MCAP is just 5x CYDY as of today
https://www.marketwatch.com/investing/stock/therf
https://endpts.com/made-in-china-taimed-wins-fda-ok-for-a-breakthrough-hiv-therapy-for-drug-resistant-patients/