So yeah - Don is eternally optimistic - and after all, that's part of his job.

 

Since I have so many transcripts - I figured - why not take a look and see exactly what he has been saying, and whether or not this seems any different.

 

So here - for your reading pleaure - is an obviously over-simplified synopsis of his statements from 2016 to present on partnering discussions, & additional indications with some notes on each talk for context:

 

Caveat:   RVX was Founded 2001.   I only ever started doing transcripts around 2013 or 2014 or so –AND -due to a long-ago computer crash – lost transcripts from before 2016 - unless they are in the link library somewhere. So this is admittedly a limited sample – but it does cover a few recent years. Also - no affiliation w/the company, and not my job, and have a life - so I miss some.  Anyway, here goes:

 

A short summary of Don’s statements about Partnering Discussions, Additional Indications,  & etc.

 

Dec 2016

 

At that time they were adding sites to the study – Russia, Taiwan, etc.

 

Re-visited BoM study design.

 

US to join in on BoM.

 

Already had Hepalink as partner.

 

Had 51 million dollar loan that would mature Aug 2017   

 

                Additional Indications:

 

                Neural Fibromatosis – so apparently this was not new in Sept 2020

 

                PAH

 

                Facio Scapulo Humeral Dystrophy

 

                Calciphyaxix

 

                Fabrys

 

                Neuroinflammation

 

                Paroxysmal Nocturnal Hemoglobinuria (PNH)

 

What he said about partnerships/deals  in Dec. 2016:

 

“What we have here is a list of some of the financial options that we have in front of us and I have them listed in order of my personal preference.

 

 Co-development, RVX-208 or follow-on compounds

 

Licensing, Regional

 

Licensing, Indications

 

Partnering Arrangements

 

Private Placements

 

Public Offering Equity

 

Debt Financing

 

Of course, the best would be a co-development deal with a major Pharma, so we have somebody else paying the bills and receiving a large up-front for that. That’s the hardest one to complete, but we do continue to work on it.

 

Regional licensing deals. These are great opportunities. We have been talking publicly for about half a year now that we are very active on some of those. They’re moving along very nicely, they don’t happen overnight, but again these come with large up-front cash. You saw a similar type of arrangement when we did a structured deal with Hepalink in China. And as you recall, that the track record was pretty successful.

 

So all of these opportunities, whether it’s licensing for regional areas, or different indications as I mentioned earlier with the FSHD, that muscular dystrophy, we can now look at that as a separate business transaction licensing agreement, because it would have an alternate delivery mechanism, so it doesn’t affect the work we’re doing with cardiovascular or renal diabetes, which gives us nice extra opportunities. We have that potential also with numerous other drugs. We have seven that we actually have on our preferred list that is looking pretty strong.

 

Now we also have partnering discussions with things like first right of refusal. That would be like an M&A type of structure for someone who after BETonMACE would want to have the first right of refusal for acquiring that particular technology.  So that’s a nice opportunity for us. Again, large amounts of money up front.

 

These deals that we do work on constantly are designed to hopefully retire the debt. We can extend the debt. We can replace the debt. We have lots of options. But retirement of that debt would be the one that would probably have the most positive impact on our stock price.”

 

 

 

Dec 2017

 

FDA approvals for BoM and for CKD subtrial

 

New Zealand Kidney Trial, BoRenal Trial

 

$100 M Financing, 4 Publications, $68.8 M long term debt repaid

 

Discussion of the mechanism

 

Discusion of the pathways – ↓ complement cascade, ↓ vascular inflammation, ↑ApoA-1/reverse cholesterol transp, metabolism/delayed & ↓ oral glucose absorption, etc., ↓vascular calcification, ↓coagulation cascade

 

Supportive research from S Nicholls – Mace ↓ in patients – esp. in patients with high CRP or diabetes

 

Kam Kalantar-Zadeh - ↓ALP findings

 

Descrip of NZ study

 

Proteomics – 1,310 proteins analyzed – 288 differently expressed  in patients with CKD 

 

    152 of 288 downregulated within 12 hours of a dose of apabetalone.

 

Examples included

 

                Inflammation:    IL6, IL1A, IFNG, TNFRSF1A, CRP, TNF

 

                Cell Adhesion:   SELP, SELE, ICAM1, VCAM1,  (Cell Adhesion)

 

                Matrix Remodeling/Calcification               :FN1, MMP3, MMP10, SPP1,

 

                Thrombosis:       SERPINE1, PLAT, PLAU, FGA/B/C, PLAUR

 

Additional Indications Listed Dec 2017

 

Pulmoary Arterial Hypertension

 

Muscular Dystrophy/Facio Scapulo Humeral Dystrophy

 

Fabry Disease

 

Neuroinflammation

 

PNH/Paroxysman Nocturnal Hemoglobinuria

 

Chronic Kidney Disease (proteomic analysis)

 

HIV-1 Latency

 

What he said about partnerships/deals  in Dec. 2017:

 

Essentially nothing other than why to invest in RVX

 

No promises of partnership or even mention of discussions in that one.

 

 

 

Sept 2018

 

Fully enrolled phase III trial since Feb

 

                Stock price from Sep 17 – Sep 18 up 174%

 

                Pipeline Plan 

 

                                Acute Coronary Syndrome

 

                                Chronic Kidney Disease

 

                                Fabry Disease

 

                                Pulmonary Arterial Hypertension (PAH)

 

                                Vascular Cognitive Dementia

 

                As usual markets, unmet needs, etc. (all of the above too)

 

                Epigenetics, BET platform, blood bank, etc. (all of the above talks too)

 

                Mechanism of action (pretty much all talks too)

 

                Pathways (pretty much all talks too)

 

                Trial endpoints, analysis points, timelines committee members

 

                Discussion of CKD – rationale and etc., including proteomics slides from 2017

 

                                & adding the more graphical  slides on SOMAscan Analysis of plasma proteome

 

                                In 5 Canonical pathways:  IL6 signaling, dendritic cell maturation,

 

                                Th1 pathway, NF-k/B signaling, acute phase response

 

               (SOMAscan Analysis of Plasma Proteome in CKD Patients IPA Canonical Pathways)

 

                                That set of 3 slides was pretty impressive basically showing how Apabetalone

 

                              Cooled or altered those pathways.

 

Additional Indications List –

 

(was in the appendix that time – not in presentation  really  - same as 2017)

 

Comments on Financing/Partnerships

 

Though he went over investment highlights again and the degree of expertise on the clinical advisory board – there was no actual discussion of  partnership discussions or negotiations

 

 

 

2019  Sept, Oct, Nov, Dec

 

 

 

Sept 2019

 

                Top line results – Failed primary endpoints. Please stay tuned, as more data will be released to prove that this drug works and we still believe it will be a success. Lead investors staying in – hope retail people will too.

 

                No discussion of additional indications OR of partnerships or negotiations.

 

 

 

Oct 2019

 

                Still a short presentation due to embargo rules but will go through some things

 

                Nov 16th results to be presented, but recaped design, parameters, etc.

 

                Gave example of forest plot – showed how to read it and indicated that forest plot for BoM would look good.

 

                Reiterated good safety profile

 

                Gave examples of drugs that failed Phase III endpoints and still went on to approval (Biogen).

 

                Noted meeting scheduled with FDA, talked of bolt-on trials and other possible options.

 

                These things happen – but we will keep working on it.

 

                Proceeding with registration even without another trial is a long shot but potential.

 

                AHA and CTAD still coming, so hold on for release of data.

 

                Will have additional conf. calls after those.

 

 

 

Nov 2019

 

                Nov 16, 2019 – speaker was Kausik Ray.

 

                Went over BoM results.  Failed primary endpoints.  Did not significantly reduce the primary endpoint. Other data therefore has to be considered hypothesis-generating or exploratory...but

 

                essentially individual outcomes and subgroup analyses were more promising, esp. for patients with low eGFR, and low LDL.

 

·         First occurrence of primary endpoint. Apabetalone better, hazard ratio 0.82, upper boundary of confidence interval 1.04, p value 0.11.

 

·         First occurrence of primary endpoint with undetermined death excluded. Apabetalone better, hazard ratio 0.79, upper boundary of confidence interval 1.01, p value not given.

 

·         First occurrence of primary endpoint or hospitalization for unstable angina or urgent or emergency revascularization procedure. Hazard ratio 0.85, Upper boundary of confidence interval 1.06

 

·         First and recurrent primary endpoint events. Hazard ratio 0.79, Upper boundary of CI 1.01

 

·         Cardiovascular death or non-fatal myocardial infarction Hazard ratio 0.79, upper boundary of CI 1.02

 

·         Coronary heart disease death or non-fatal myocardial infarction Hazard ratio 0.79, Upper boundary of CI 1.02

 

·         Non-fatal myocardial infarction  Hazard ratio 0.80, Upper boundary of CI 1.08

 

·         Cardiovascular death Hazard ratio 0.81, Upper boundary of CI 1.19

 

·         Stroke  Hazard ratio 1.01, Upper boundary of CI 1.98

 

·         All-cause mortality  Hazard ratio 0.88, Upper boundary of CI 1.24

 

·         First hospitalization for congestive heart failure Hazard ratio 0.59, Upper boundary of CI 0.94  *

 

Still encouraging, well-tolerated, slightly lower event rate, underpowered to show significance at that level, warrants further study.

 

Obviously no discussion of other indications or partnership negotiations

 

 

 

      Nov 18, 2019 – Speaker was Don

 

      Despite failure on primary endpoints, development of Apabetalone will continue

 

Discussions with FDA ongoing – looking to see if they can get breakthrough therapy designation

 

In terms of cardiovascular results, if they had counted CHF instead of stroke in MACe,

 

        BoM would have met its primary endpoints. In terms of the individual endpoint s

 

        It achieved significance for Non-fatal MI,  and CV Death, two of the three MACE points.

 

Forest plot looked good. Eleven of twelve pre-defined hazard ratios improved with Apabetalone.

 

CHF improved significantly.  So re-defined 3 point MACE would have worked.

 

Pre-specified subgroups -  helps patients with low eGFR, no effect on normal –

 

That was presumably a good thing, not an artifact. Low eGFR is assoc w issues like inflammation, coagulation problems, etc. that are not present in normal eGFR – so no effect on healthy patients if anything could be an indicator of safety, whereas statistically significant benefit accrued to patients with low eGFR.  

 

Aside from the fact the Apabetalone was significant for patients with low eGFR – it was synergistically beneficial in combination with SGLT2 inhibitors, GLP1 receptor agents, and DDP4 inhibitors.

 

Also significant hazard reduction in patients with low LDL

 

Gave specific example with Apabetalone and SGLT2 inhibitor Jardiance by Eli Lilly and Boehringer Ingelheim.

 

Talked about CTAD conf which was still coming up – data embargoed but stay tuned also good news.

 

Other indications – Not disscussed

 

Partnering Discussion:

 

Two major statements on this:

 

“This basically confirms that we did miss the primary endpoint barely. But we have very strong trending data and it’s crystal clear how we move this drug forward for approval. And we can plan around things like that 5.8% event rate instead of the 7.5. We know it’s there now. And we also know we have a huge benefit from it being the SGLT2 category. So just to remember in following up on this, the narrow MACE with CHF would have been highly statistically significant. And we can move forward, and will move forward  with plans to show just that. The renal subgroup below 60 GFR baseline had phenomenal data, again highly statistically significant, and lots of categories to encourage co-development with that one as well. And Apabetalone with SGLT2 inhibitors, very exciting data. Synergistic data. And obviously we will be in discussions moving that one forward as well.  “

 

AND

 

“OK, let’s move to the final main slide here now, the near term commercialization steps. Now we kind of have a five-point approach here that we’re following and this is what we’ll be doing over the next few months. One of the key areas is the breakthrough therapy status filings, and we’ll be doing that both at the FDA and EMA. We believe we have what it takes to get that done in the next 90 to 120 days. And we’ll be moving forward in that type of direction regardless. So, SGLT2i partnering discussions, one is already initiated and key patents have already been filed. That is an exciting category. Renal partnering and discussions are moving forward. Congestive heart failure partnering discussions, already initiated. And we will continue with our orphan partnering discussions but we’ve narrowed it down to two only at this time just to stay focused. And they will be PAH and HIV only at this time. The PAH enrollment has already commenced. And the HIV funding has been derived and yet to be named yet [sic] from a US organization.  So going forward, these five areas are going to add a lot of commercial value in the very short term. “

 

 

 

Dec 2019

 

Apabetalone showed significant improvement vs. placebo & standard of care for patients with a baseline MoCA (Montreal Cognitive Assessment) score below 22.

 

For this group,  158% relative improvement in cognitive function over standard of care plus placebo was reported.

 

Significant and trending changes across treatment also showed in ALP and HDL

 

No significant change was noted in those with baseline between 22 and 26 or > 26 although the mildly cognitively impaired showed a trend toward improvement (those with baseline scores of 22-26)

 

        (need to check that – because i thought i remembered a non-significant wiggle toward a lower score for the middle group)

 

Acknowledged that this could have been an accidental breakthrough, but it is worthy of further study. The BoM population had a higher rate of elderly, CKD Diabetes, and CVD patients – and those are all risk factors for cognitive impairment – so the patient population is suited for the question –

 

        In addition – dementia can be caused or exacerbated by transcriptional disturbances at epigenetic levels – which is where Apabetalone helps – so it makes sense to look at this.

 

Other Indications and Partnering  Discussions were almost combined into one section of this talk, as follows:

 

“OK, so on slide 14 we have our near-term commercialization steps. And this is our multi-point approach to progressing the corporate and commercial valuation of the company.

 

As we’ve mentioned before, we’re applying for breakthrough therapy status with both the FDA and the EMA. The process will take 90 to 120 days.

 

We’re continuing our SGLT2i partnering discussions. And we’re very excited about the potential there.

 

The renal partnering discussions are ongoing.

 

Congestive Heart Failure partnering discussions are ongoing as well, with multiple parties.

 

Orphan partnering discussions have been in both PAH (pulmonary arterial hypertension) and HIV. We will limit it to those at this time, just to stay focused. And the PAH enrollment has already commenced. The HIV funding is expected to be announced about mid-year.

 

And then of course after today’s announcement, I will be proceeding further with MoCA partnering discussions. And we’re quite excited about where all this is going, especially in a field like cognitive function, where you really just don’t see results that are 158% improved over treated groups. These results need to be confirmed and validated and moved into the traditional Phase 3 type of approach. But regardless, this is a field that does not see subgroup categories like this and we’re quite excited about moving this forward.”

 

 

 

June 2020

 

50% reduction in MACE events in CKD patients, 63% reduction in MACE events when combined with SGLT2 inhibitors.

 

First-ever evidence that a drug of any kind could reduce MACE and hospitalization for CHF.

 

Addreseed large sell-off by hedge fund

 

Breakthrough therapy designation awarded in February 2020

 

Additional  Indications

 

COVID & maybe seasonal flus

 

Not an antiviral, but a lower viral load due to ↓ability to replicate

 

“The consortium’s tests were done in Vervet – that’s an African Green Monkey, which is an animal that Resverlogix has extensive experience with. We’re also aware that the Vervet’s bromodomain system is differentiated from [that of] humans. Therefore we compiled our extensive data and applied for COVID-19 study funding from various groups. With third-party funding in place now, we are currently moving forward with studies on human lung and related human lung tissues”

 

Re PAH

 

“We have already completed treatment of some patients in our Quebec Center; in our Calgary site paperwork has been completed and [the study is] ready to progress. We have not witnessed any health-related problems to date. Unfortunately, as of March 2020, both sites, Quebec and Calgary, were side-lined due to COVID 19. They are still in lock-down since the start of the pandemic; however, both are expected to open soon, and we will continue with this program.”

 

Partnering Discussion Statements

 

“Both of these major advancements have allowed us to expand our various partnering discussions with major pharmaceutical companies. Much of what we have in progress, I still cannot share due to related sensitivities. I will explain some of these sensitivities as we proceed today.”

 

AND

 

“Now this brings us to our discussion about our current business plan and go-forward model. As many of you already know, Resverlogix currently meets all of the general parameters of a successful pharma partnership: efficacy - pre-specified results from BETonMACE; safety - 1900 patients have been dosed and FDA reviewed; regulatory approvability – that’s evident in the FDA breakthrough therapy designation status; Understanding of the Mechanism of Action – we have in-depth knowledge and publications, we have 60 publications now; and a strategic commercialization plan.

 

Collectively we have a solid program that has attracted the attention of several pharmaceutical groups. As the final Phase III registration trial will be expensive, we have decided to partner with a major pharmaceutical group at this development and commercialization point. The pharma will be responsible for funding the trial and operations. Discussions are going very well, and upon completion, the future of Resverlogix will be very solid. Continuing discussions will be adding the new data and its commercial implications, as well as FDA planning and approval information.

 

Until such time as we can confirm a partnership, we will continue to fund the company internally and through whatever other methods may become available to us.”

 

 

 

Sept 2020

 

Apabetalone has breakthrough designation. FDA could decide to register even halfway through trial if results are good enough. 

 

Apabetalone lowers MACE in CKD patients and shows synergy with SGLT2 inhibitors. Etc.

 

Discussion of trial plans to include SGLT2 in trial, more CKD patients, etc.

 

All the usual stuff – mechanism, markets, publications, safety, etc.

 

Additional Indications:

 

NAFLD/NASH

 

Neuro fibramatosis

 

PAH

 

Muscular Dystrophy

 

Fabry

 

COVID

 

and more (not listed)

 

Partnering Discussions

 

“So moving forward, we have several development approaches.

 

Our first development approach is actually partnering this with a major pharma. We see this as a very high likelihood at this point. We would be receiving a major up-front this year. This is finalized ... [TRANSCRIBER’S NOTE: I listened several times to this sentence, but did not hear “If” this is finalized or “As” or “When” or “Once”– but the recording is a bit glitchy – so use your own judgement about this. Clearly “This is finalized” has a different meaning than “once this is finalized” or “if this is finalized”, and I was not sure – given that other options are still discussed] ...and the company we’re partnering with would also be paying for the entire Phase III B trial. So this is a big step forward for us to be able to advance and reduce costs in such a significant way.

 

So the new partner would also include their SGLT2 inhibitor in the program. So they effectively will have the only combination data going forward to advance into new medications, and our data has shown strong synergy with the SGLT2, so it will give our new partner a very solid market position. And we’re proud to be able to present that as an opportunity.

 

And going forward we also would have milestone payments and M&A options based on the results of this particular trial.

 

So it’s a very good design. It’s a very equal design for both the pharma and the biotech, being us. Whereas depending upon the results of the trial, if it’s really solid we get paid more. And if it’s just ok but passes, the pharma isn’t paying too much. So it’s a good setup.

 

The second option is actually we can sell or trade off some of our future royalty rights to pay for the trial and include ourselves if we wish.

 

We also have a third option where we can work with existing and new investors to do this on our own.

 

I personally think Option 1 is the best - to team up now with a multi-national global pharma company that has weight in the field and sales people in the audience already and uh, in the field already. “

 

AND

 

“Now as far as business strategy, we already have a partnership in Greater China, Hong Kong, Taiwan, and Macau. That is with ShenZhen Hepalink. They’ve been an excellent partner. Since working with us from day one they’ve increased their holdings up to 130 million dollars. And so we have a good partner, a good development group going on there.

 

We’ve also licensed in Israel.

 

And we’re in discussions with other global deals regarding licensing and/or co-development partnerships as mentioned earlier. “

 

AND

 

“We have multiple partner partners we’re discussing in multiple different formats. And I can say as of yesterday I’m very pleased with where we are and with how fast this is moving. We will see activity before the end of the year.”