Innovation Pharmaceuticals Inc (IPIX)

[TOB]

This was also emailed from the CEO.

[It is the raw notes from a meeting attended by Cellceutix’s President and Chief Scientific Officer Dr Menon and Dr Alexander, MD, MPH, former Chief Operating Officer who now remains as an a consultant to Cellceutix.

The company has previously made a Press Release that: Cellceutix Plans ClinicalTrial in Patients With Ulcerative Proctitis So this is public information. These notes give insight to the ongoing planning for this planned clinical trial. Despite having 3 drugs in clinical trials for 4 indications, and more trials expected, CTIX is obviously aggressively exploring additional clinical trials and indications to target. This strategy IMO reduces risks to shareholders by giving more chances of success.

This is fascinating stuff, as it gives insight to the active exploration of the use of Brilacidin, now being tested for Oral Mucositis, for other inflammatory diseases along the alimentary tract. This is a huge potential market. If Brilacidin-OM shows efficacy for Oral Mucositis, the implications are it should be explored for Ulcerative Colitis. First as a topical application for Proctitis, the distal form of Ulcerative Colitis.

I’ve added text in [brackets] to clarify some of the acronyms used. Any errors mine. – TOB]

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Notes from 04 Dec 2014 Meeting with UC [Ulcerative Colitis] thought leaders

Krishna Menon and Jim Alexander (Orlando)

KOL participants

XXXXX 5 GI Key opinion leaders

B – brilacidin

4% acetic acid in rat colon is not standard. Use TNBS or knock out mode (GL)

Udragit release (GL)
MDR gene is predictor of response to steroid in UC [Ulcerative Colitis]

Consider indication of radiation [induced] proctitis with prostate radiation, or cervical [radiation therapy]

cancer radiation – use B [Brilacidin] suppository all during radiation

Yarelsburg has published on use of sucralfate in radiation proctitis

XX has done 100 trials, IBD [Irritable Bowel Disease] phases 1 to 4 big practice.

XX – mesalamine just enrolled 15 quickly , interested in slow growing

mycobacteria as origin of Crohns.

XX at USA, 8---9 NDAs, FDA interactions, lots of bowel prep studies
XX at U of XX. Can’t do quick studies there. 3500 pt with IBD [Inflammatory Bowel Disease]. He has been on FDA
Advis comm. [committee] Very well published. XX at XX interested in gut microbiome, have a number basic science R01 grants. He only does IBD. Spends 80% of his time with patients.

XX in XXX. now with 80 GI docs. At XX 8 yr then private practice. On lots of
committees with XX.

XX – unmet need, must consider ‘diversion colitis’ rectum inflamed after
ileostomy surgery for IBD. XX says was a NEJM article on butyrate enema and this
smells bad, XXX mucomyst is a free radical scavenger, and this is used. XX sees
about 2---3 of these patients every 5 months. It is orphan indication. Nothing is
approved for diversion colitis [inflammation of the bypassed colon following surgery] . they usually use 60 mL BID and then every 3 days.
(not sure what?)
SIBO (not sure what this is)
Discussion of diverticulitis being an inflammatory disease and no need for
antibiotics, maybe a one IV dose of B [Brilacidin] would help acute diverticulitis. This is an inflammatory disease.

SCAD is ‘segmental colitis associated with diverticulosis’ a new entity
XX noted 75% rifaximin response, lactulose test not predictive. Target 1, 2, 3, ?? not sure what this means.
Asked about C diff. we said B [brilacidin] had no activity. Fidoxamine $2400 for 10 days. XX
can get rifaximin for 3 cents a dose from Pakistan.
Salix just had budesonide foam approved (Uceris) the foam will reach 40 cm. the
suppository only 15 cm of rectum.
With UP [Ulcerative Proctitis] or UPS [Ulcerative Proctosigmoiditis], the disease does not go away, need maintenance therapy.
Niche for B could be between mesalamine and steroids.

Some KOL support for trying a single IV dose of B in these conditions. Many
patients don’t like enemas.
XX thought with left sided UC, give a single IV dose of B
The 5 –ASA market is $900 M (GL)
50% of patients with proctitis have extension beyond the rectum.
Most patients would want a pill and not an enema.

Some KOL support to try topical B [Brilacidin] first. Use Mesalamine failures (no definition of
that discussed). ‘Useris’ – is this the trade name for the Salix drug.
The median age of someone with left sided UC [Ulcerative Colitis] is 29 years. Disease needs
maintenance therapy
No major safety concerns with mesalamine – rate of interstitial nephritis is 1/500
(GL) this is an idiosyncratic reaction. See Cochrane Review for mesalamine.

XX talked about rectal tacrolimus suppository, sucralfate mixed with aloe vera.
Niche of B is avoid steroid enemas !!! (Important)
Foam will go up to 40 cm (See Uceris PI)
Indication could be acute treatment of ulcerative proctosigmoiditis

Microbiome is a hot topic
IS would not use IV Brilacidin in proctitis–go with topical.
Stelara is testing in IB with a single IV dose followed by sub cut.

Re study [Proposed Clinical Trial]– open label design
Enroll 30% with proctitis only, 70% with UPS [Ulcerative Proctosigmoiditis]

Note the UCEIS (Ulcer colitis endoscopic index severity)XXXXXXXX.

Need to see mucosal healing as endpoint.
Do a series of 5---10 patients at various doses
XX if you gave a dose, you could see some effect 5 days later, but patients don’t
want to be scoped frequently – XX says that do symptom score and scope at 4
weeks

Calprotectin test on stool from Quest is the hot thing, normal is 169 or below,
colorimetric test.
The Mayo clinic scores are used, but the modified that removes friability is
supported by XX. See literature.
Use MMDAI criteria and the UCEIS

XX–do scope at 0, week 4, week 8, CRP [C-Reactive Protein] will be up in 50% of patients. If normal is
5 –many of these patients have CRP of 100, but takes a while to come down,
unless give monoclonal.
Do calprotection at 0, 2,4,6,8 weeks
With budesonide MMX, 20% had normal biopsy
Recommend 2 rectal biopsies and 2 sigmoid biopsies at enrollment, just hold
them for use later to explain results. Do not wait for bx results to enroll.

Do not exclude smokers
No NSAID
Mild moderate via the Mayo score of 4 to 8 on endoscopy
MMDAI is also 4---8
Add the UCEIS
You want active disease, outpatients, no TNF ever
Endpoint is mucosal healing
No central reader for POC [Proof of Concept] study, take pictures

No prior dysplasia
No Crohns serology +
No indeterminate
No immunomodulator
No hx of C diff in past 12 months and neg C diff at enrollment
Negative enteric pathogen and O and P at enrollment

DW can do this study, IS can do this study . 2 sites enough

IS can get calprotection test for $60, retail is $250

Decision at Cellceutix
Formulation – most likely enema, but this will not extend to 40 CM
So maybe just do proctitis in POC [Proof Of Concept] study, not sigmoiditis
Doses to use, open label, why not several doses, once daily , twice daily
maximum.
Evaluate at 4 weeks and 8 weeks. Optional scope at 2 and 6 weeks for patients
who agree.
Biomarkers – calprotectin, CRP