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There was a discussion earlier in the week with regards to T+2 or T + 3. My understanding is that if you want to benefit from Accustem shares you would need to purchase on Tuesday at the latest (I am assuming anytime before 4.30pm).
Weds and Thurs would be pretty benign days, you wouldn't buy given you have missed the Accustem deadline, would wait till Friday. Might drift lower if US sells keep ticking over. I was of the view Friday am was the date at which people could sell and still benefit from the Accustem shares, but others have suggested Monday 2nd...
Would appreciate view of others...

Afternoon all,
I posted the info below a month or so back, just thought it might help with thread...apologies for the naval gazing if already seen...

Exact and OncotypeDX...not seeing how we get to an approx valuation given lack of competitive strength and cash impact) but might be of interest??
- Genomic Health when purchased had 800 emps and turnover was $223mn in H1 of that year...this wasn't all Breast cancer related, $162mn was so had other diagnostics being developed at the time.
- OncotypeDX covers Colon and Prostate Prognostics aswell (under Oncotype umbrella)
- At that time, revenues had grown c. 20% y-o-y $330mn to $400mn.
- They did 39k tests in that last quarter so run rate of c 160k tests per annum.
- It looks like each test sells for $3.5-4K, but looking at their sales, get a unit price of $2k coming to Exact so assume remainder is in the field pricing.
- Exact paid $2.8bn which is well documented, and turnover was c 400mn USD at the time.
- Exact selling into 90 countries and looking at their recent figures sales seem flat at 160k per annum.
- For info, c 2nn women a year are diagnosed with breast cancer which in my view is pretty high reach at 160mn tests.
- I assume growth in sales is dependent on proving a TCO that it is of more value to use the OncotypeDX tool as it would lead to a better result for the patient but also (and unfortunately the case) is more cost effective for the healthcare trust.
- Of exact sales, 72% in US, 28% elsewhere.
- Now trying to expand into Europe where previously weak, and where TILS should have strength, particularly UK and IT.
Of interest, 160k breast cancer tests, but doing 1.7mn colon tests.
- Exact would have been buying the skill set to expand Prognostics not just in breast cancer but wider oncology. I would assume similar process to identify markers of other cancers so once you have the proprietory technology should be a wider market to aim for, and suspect that is where the Exact Sciences business saw the scope from the acquisition.
- I can't ascertain profit relating to Oncotype as it is bundled but will have a dig around to see if I can find anything.

- Interestingly Exact presented at ASCO 2020 aswell and as you would expect are looking to improve the efficacy of their models/tools.

Two key elements on treatment, cost being one unfortunately and drug costs shown by BMO3 so PCT can direct it's spending better, and secondly, saves someone going through extensive treatment when it might not have been necessary / best course of action.

Morning All,

Would be good to get your opinions on the likelihood of Foralumab delivering strong results in the Brazil Trial…

Risk goes with the territory in BioTech, but would be good to get the thoughts of others…(esp. Shiraz and Wisha given pharma knowledge)…

I’ve put some initial notes below..

We know it’s the only fully humanised Anti-CD3 mAb

We know Phase I oral admin of Foralumab was well tolerated (in healthy volunteers), so we don’t have the toxicity risks of IV.

Previously been shown that orally administered Foralumab to humanised mice (which have human immune systems) with skin grafts tolerated doses and prevented skin xenograft rejection indefinitely
Clinical study (don’t think TILS) indicated that oral administration of OKT3 (mouse based Anti-CD3) was well tolerated at 1 mg/day for 30 consecutive doses in patients with moderate-to-severe ulcerative colitis. Importantly, the treatment resulted in clinical responses in 3 out of 6 patients, including one patient with a complete clinical response. (OKT3 is Muromonab-CD3, been around for years and is approved for the therapy of acute, glucocorticoid-resistant rejection of allogeneicrenal, heart and liver transplants).

So given fully human, lack of toxicity and clinical response in Colitis (managing autoimmune reaction / cytokine storm), shows great promise.

In 2007-09, pre-Foralumab being owned by Tiziana (owned by NovImmune), a phase 2a IV based clinical trial with 12 patients, based on analysing autoimmune reactions on renal transplants. Also, 40 patient Crohns disease phase 2a. Again IV and humanised mouse, but can’t trace outcome of these studies.

However, Visilizumab (Humanised Anti-CD3) seems to have had issues with toxicity (assume due to humanised element and IV) but also with efficacy.

Otelixizumab seems to have had limited efficacy and not aware of any ongoing trials in the last 3-4 years.

Teplizumab – seen results for Diabetes - slowed progression to clinical type 1 diabetes in high-risk, nondiabetic relatives of patients with diabetes who had at least two autoantibodies and abnormal results of an oral glucose-tolerance test at trial entry.

Above just my musings and may have missed other things....

Cont...
Humira (Adalimumab) is a fully human monoclonal antibody (fully human do exist in Anti-IL6, not in CD3 where Foralumab is the only one). The market size for this is massive…Abbvie’s Humira accounts for $19bn of their $35bn turnover, which clearly has been very successful…but has significant side effects. As of last year, they are starting to see a fall off in revenue, and last year diversified by paying $63bn for Allergen to expand their portfolio…in part down to the expected continued drop off in Humira revenues. This is expected to accelerate given Humira copycats in the U.S. are available from 2023.

If you could develop a non-IV, less toxic, lower concentration offering available as oral or nasal, it would make sense to seek to progress that in order to create a differentiator in the market, protect your very significant revenues and maintain a competitive advantage when the market opens further in 2023 when patents expire.

In terms of other Anti-IL6 products in the market…

Actemra (Roche) (tocilizumab) – humanised mAb - £2bn per annum, 8% y-o-y growth

Remicade (J&J) (Infliximab) - humanised mAb - £3bn per annum, -18% y-o-y growth

Kevzara (Regeneron) (Sarilumab) – fully human mAb - £200mn, 40% y-o-y growth

Remicade sales falling for Janssen (J&J) due to increased discounting to combat competition from bio-similar offerings…again, need to find a way to re-establish a competitive advantage.

On a wider note, and previously mentioned on this board, Regeneron and Sanofi developed a drug (in practice, a ****tail – not been able to track details of any detail on what is in the ****tail…kind of understandable…) for the treatment of rheumatoid arthritis, and looked at it for Covid-19, but stopped the phase 3 trial in July due to adverse reactions. Various potential reasons for this e.g. stage of illness at which it was administered, but again, anything that reduces concentration / toxicity, and has a localised delivery can only improve the potential for treatment of respiratory illness, whether Covid-19 or the next that comes along (while Covid-19 is a novel scenario to most western countries…not really the case elsewhere…(Sars, Swine Flu, Mers, Bird Flu…and that’s just in the last two decades) so finding better ways to handle Cytokine storm isn’t going away after Covid)

The potential here is huge…whether pharma are looking for a differentiator (and cost upside) for protecting revenues or looking for the next innovation to target inflammatory illnesses, pandemic origination or otherwise…get this right (and that’s not a given) the opportunity is mind blowing…

Some great posts again last couple of days, thanks for the links...
Some more thoughts below, would appreciate others critiquing…

When the half year RNS came out, majority of the info was known to LTH’s, but was drawn to the following…

“Research is planned to extend the intellectual property on our innovative lyophilized foralumab antibody powder in enteric-coated capsule platform technology to other anti-TNF monoclonal antibodies, namely adalimumab (Humira®) and infliximab (Remicade®), as well as anti-IL6R mAb (TZLS-501).

Additionally, lyophilized antibody powder of adalimumab will be tested for efficacy in a validated mouse IBD model.”

(TNF is tumour necrosis factor and links into cytokine inflammatory issues associated with arthritis, Crohns etc… but also CV19)

Noted that you picked up on the same paragraph SK!

So thought I’d do a little digging into it…below is skewed towards TZLS-501 but some can be applied to Foralumab aswell…and the patent there is broader than the one for TZLS-501.

As we know, TZLS-501 is an Anti-IL6, with patent approval on the 24th August. Trial for aerosol treatment planned for Q1 2021.

In Tiziana’s 29th June 2020 RNS, it stated that…”In receptor binding assays, TZLS-501 is considerably more potent than the other anti-IL-6R mAb in this class, such as Actemra”

While both are Anti-IL6 (and will come onto other Anti-IL6 drugs in a minute), there is a key difference.

Taken from their patent…”Unlike antibodies that bind to IL-6 or IL-6R individually, for example, in the groove where IL-6 binds to IL-6R, the antibodies of the TZLS-501 Patent approval invention do not inhibit or otherwise interfere with the interaction between IL-6 and IL-6R to form the IL-6Rc complex.”.

As a result…in some modulations, the concentration of the TZLS-501 Mab’s can be up to 100 times lower than the concentration needed from other antibodies. Coupled to this is that the intention is to deliver it in a nasal / aerosol mechanism rather than IV. So, easier to administer, cheaper, less toxic…less side effects…quite compelling!

While I don’t envisage Tiziana seeking to compete directly in this space, the technology would lend itself to either being sold or more likely licenced to big pharma.

Why would it be of interest to them? Let’s look at some of the biggest players in the Anti-IL6 space…(again, has overlap with Foralumab and Anti-CD3)

Humira (Adalimumab) is a fully human monoclonal antibody (fully human do exist in Anti-IL6, not in CD3 where Foralumab is the only one). The market size for this is massive…Abbvie’s Humira accounts for $19bn of their $35bn turnover, which clearly has been very successful…but has significant side effects. As of last year, they are starting to see a fall off in revenue, and last year diversified by paying $63bn for Allergen to expand their portfolio…in part down to the expected continued drop off in Humira revenues. This is expected to accelerate given Humira copycats in the

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