Ann: ANP Updates on US Regulatory Plans for ATL1102 in DMD, page-149

The waters have been muddied a lot post this last announcement. I dont think a lot of this is justified. Going the through the announcements, a better picture of what happened in the 2017/2018 FDA decision WRT dose amount for MS can be found:

ATL1102 for Multiple Sclerosis Phase IIb trial Update
Antisense Therapeutics (“ANP” or the “Company”) wishes to advise that the Company has been in recent
communications with the US Food and Drug Administration (FDA) in regard to the ATL1102 for Multiple Sclerosis
(MS) Phase IIb IND application. The FDA has told ANP that modifications to the proposed clinical trial are needed in
order for FDA to clear the IND to proceed. In a recent teleconference with ANP, FDA provided a high-level description
of the necessary modifications and will provide actionable details in a formal written response to ANP by late August
2017. During this period of clinical hold ANP will formally submit updates to the IND soon after receipt of FDA’s
written response and the FDA has 30 calendar days to review and potentially clear the IND.
In parallel, the Company is progressing its grant application with a US Federal Agency, the National Institute of
Neurological Disorders and Stroke (NINDS), part of the National Institutes for Health (NIH) where ANP’s clinical study
synopsis for the Phase IIb study passed through two levels of feasibility assessment. The Company now plans to
modify the proposed study design to align with both the anticipated FDA requirements noted above and feedback
on the trial received via NINDS interactions. The next step will then be submission to the NINDS Extramural Science
Committee (ESC) for review and potential approval to move forward to lodging of the full grant application.
The Company advises that its application to conduct a clinical trial of ATL1102 in patients with Duchenne Muscular
Dystrophy (DMD) at the Royal Children’s Hospital in Melbourne is ongoing. The Company is currently addressing
questions received in line with the hospital’s approval process. (27 July 2017)

ATL1102 for Multiple Sclerosis and Duchenne Muscular Dystrophy Update
Antisense Therapeutics Limited (“ANP” or “the Company”) provides the following update on the progress of its
Multiple Sclerosis and Duchenne Muscular Dystrophy programs.
Multiple Sclerosis Program
Following the FDA’s partial clearance of the Company’s proposed Phase IIb clinical study of ATL1102 for Multiple
Sclerosis (MS), ANP’s US regulatory advisors lodged a submission on behalf of the Company for a meeting
request with the US Food and Drug Administration (FDA) to clarify criteria under which MS patients could
receive higher doses of ATL1102 in the Phase IIb study. The FDA has subsequently advised that the most
efficient path forward for the Company is to submit a complete written response to the partial hold outlining
ANP’s proposed changes and inclusion of additional safety related parameters to the Phase IIb clinical study
protocol that would potentially allow for the administration of higher doses. The Company anticipates submitting
its complete response early in the New Year. The FDA would then have 30 calendar days from submission to
respond to the letter.
Duchenne Muscular Dystrophy (DMD) Program
As previously advised, ANP is planning to conduct a clinical trial of ATL1102 in DMD patients at the Royal
Children’s Hospital (RCH) in Melbourne.
Through consultations with the Principal Investigators of the trial, who are clinical experts in DMD, and their
interactions with the RCH, the Company is now proposing an important change to the clinical trial protocol - to
extend the dosing duration of the study from 8 weeks (as per the currently submitted dose escalation study
protocol) to 6 months.
The extension of the dosing period may allow for ATL1102 to show an improvement in key clinical endpoints
that are relevant to DMD disease progression (e.g. the upper limb function of the boys), generally only
observable in longer term studies, and of the type that would be required for future product registration. Dose
modelling predictions of the use of ATL1102 in a 6 month MS study (Guzy & Bauer)** lend support to the
potential activity of this intended dosing regimen for the DMD trial. This would be an initial single dose study
of 25mg of ATL1102 per week in wheel chair bound boys weighing between 30 to 60kg.
This new trial protocol is in preparation for submission to the Human Research Ethics Committee of the RCH
for review at their next meeting on 5 February 2018. Further details on the trial will be communicated in news
regarding trial approval. Notably, the change to a single dose administered over 6 months will have no material
impact on the study cost or timeline estimates compared to the 2 month escalating dose study design.
As previously advised ANP is assessing options to access additional capital to fund the value adding activities
described above. The Company continues to investigate and apply for non-dilutive grant funding opportunities
extending now to the new DMD program. Market interest in new DMD treatments is very high. Accordingly the
Company anticipates pharmaceutical company partnering interest as further clinical development
advancements are made in our DMD program. (19 Dec 2017)

Institutional Placement and Rights Issue
 Transformational capital raising backed by leading institutional investors including Australian
Ethical Investment, Platinum Asset Management and CVC Limited.
 15% Placement to Australian Ethical Investment together with a proposed Entitlement Issue
to shareholders to raise up to A$5 million.
 Australian Ethical Investment and Platinum Asset Management expected to become largest
shareholders in the Company with up to 19.99% and 5.6% respectively.
 Funds raised would be utilised to complete and report on ATL1102 Phase II clinical trial in
Duchenne Muscular Dystrophy patients, initiate the ATL1103 Early Access Program in
Acromegaly and fund operations into 2020 based on current cash flow projections.
Antisense Therapeutics Limited (“ANP” or the “Company”) is pleased to announce that it has received
strong financial support from a number of leading healthcare institutional investors to undertake a
Phase II clinical trial of its immunomodulatory therapy, ATL1102 in patients with Duchenne Muscular
Dystrophy (DMD), an incurable muscle wasting disease of children.
The capital raising is to be conducted via a placement to Australian Ethical Investment utilising the full
15% placement capacity limit available under the Listing Rule 7.1 via the issue of 24,233,911 shares
at $0.024 to raise A$581,614, followed by a proposed 1:1 Entitlement Issue to all shareholders at the
same price to raise up to $4.5 million.
Australian Ethical Investment, Platinum Asset Management, CVC Limited, Leon Serry AM and others,
have indicated their support and intention to subscribe to part of the offer via commitments to shortfall
shares becoming available following the take up of entitlements by shareholders. Australian Ethical
Investment and Platinum Asset Management expected to become largest shareholders in the Company
with up to 19.99% and 5.6% respectively. Further details regarding the Entitlement Issue will be
released shortly.
XEC Partners has been appointed as Lead Manager for the Capital Raising.
The funds raised will be utilised to complete and report on the ATL1102 Phase II clinical trial in
Duchenne Muscular Dystrophy patients and to initiate the ATL1103 Early Access Program.
Following receipt of approval from the Royal Childrens Hospital (RCH) earlier this month, ANP will be
conducting a 6 month trial in patients at the RCH neuromuscular centre, which operates the largest
clinic in the southern hemisphere treating children with DMD. Patient enrolment is currently anticipated
to commence in May 2018 and based on current study timeline projections, dosing of patients is to be
completed by Q1’19 with study results to follow in Q2’19.
The new funding will also be used for the formulation of ATL1103 (or atesidorsen) raw material into
injectable product, scheduled to commence in May 2018, for the potential treatment of approximately
15 acromegaly patients for 1 year under an Early Access Program (EAP) within select countries of the
European Union. The Company aims to initiate EAP in 3’Q’18. Under the EAP, the Company can set
pricing for the drug. The current average cost of required treatment for these patients in Europe is
approximately A$80K per patient per annum (3 Apr 2018)


ATL1102 in MS
• Phase II clinical trial
completed
• Monitoring data from DMD
trial to inform on future
clinical development in MS (29 Nov 2018 AGM presentation)


ANP’s current development focus is directed towards the clinical development of ATL1102 in DMD. ANP believes, though, that circumstances could present in the future where the Company has the capacity and justification to continue to invest in the further clinical development of ATL1103, including activation of an EAP. Until that time, the Company will not apply further resources to the EAP process and will continue to direct its focus and funds on the ATL1102 for DMD program and the ongoing Phase II clinical trial, where dosing of all patients is to be completed in early November 2019. (announcement 26 Aug 2019)

US FDA Grants Rare Pediatric Disease Designation to ATL1102 for the treatment of DMD
• Potentially eligible for rare pediatric disease priority review voucher (PRV);
• PRV may be utilised to expedite marketing authorization review by FDA; or
• PRV may be sold to provide additional non-dilutive capital
Antisense Therapeutics Limited [ASX:ANP | US OTC:ATHJY] is pleased to advise that U.S. Food and
Drug Administration (FDA) has granted rare pediatric disease (RPD) designation for ATL1102 for the
treatment of DMD, a rare and fatal muscle wasting disease where inflammation in the muscle leads to
fibrosis and death of muscle tissue.
As part of advancing US regulatory strategy and recent application to US FDA for an Orphan Drug
Designation (ODD), a request for a rare pediatric disease designation was submitted in conjunction
with the ODD application. The FDA has granted the designation of ATL1102 as a drug for a rare
pediatric disease following submission of data from Phase II clinical trial of ATL1102. The FDA has also
determined that DMD meets the definition of a rare pediatric disease based on the information
submitted by the company and reliance upon additional supportive information. Therefore, FDA has
determined ATL1102 to be eligible for rare pediatric disease designation for treatment of DMD.
Further, under the FDA’s Rare Pediatric Disease Priority Review Voucher Program*, a company that
receives an approval for a product designated for a rare pediatric disease may qualify for a voucher
that can be redeemed to receive an expedited priority marketing authorization review. The award or
non-award of a rare pediatric disease priority review voucher is made at the time of marketing
approval, should the Company request such a voucher in its marketing application, and subject to it
meeting the eligibility criteria for a PRV. Priority review can cut the FDA review process by as much as
4-6 months, shortening the time it takes for the drug to reach the market.
The sponsor of a rare pediatric disease drug receiving a priority review voucher may transfer or sell
the voucher without limitation, subject to applicable FDA requirements for filing and use. An intangible
benefit of the voucher is the value created for a company if the faster review leads to an expedited
approval and therefore provides a commercial advantage via earlier sales of a new drug on the market.
In recent years, a secondary market for the vouchers has emerged allowing companies to use the sale
of PRVs to recoup expenses undertaken for drug research and development and present them with
additional source of non-dilutive capital to support further advancement of clinical development. Since
2009 when the first PRV was awarded the values for these vouchers have ranged between US$68
million and US$350 million.
Mark Diamond, Chief Executive Officer of Antisense Therapeutics said: “We are very encouraged by
the granting of the rare pediatric disease designation to ATL1102 by the FDA, which recognizes a great
need for new and improved therapies for boys with DMD. We look forward to future interactions with
FDA as we refine our strategy for development of ATL1102 in DMD in the US.” (30 Sep 2020)

ANP is a small drug discovery biotech with limited resources. It must always drive to get maximum bang for the buck. The initial phase 2 trial into MS showed that ATL1102 showed promise. This lead to the investigation of a trial into DMD. The FDA had put a limit on dose size to 25mg until more data was provided . ANP pivoted research into DMD boys weighing 30kg to 60kg where this dose amount was thought to be effective. At the same time they were investigating a EAP of ATL1103 into Europe with global agreement signed with MyTomorrows in the Netherlands. Although the ATL1103 was produced, this agreement never materialized due shifting goalposts. But it would have been a low cost way of finding revenue if it had worked out.
The EMA has shown that it can see ATL1102 used at a higher dose size, with no extra research required. So ANP is actively perusing a phase 2b trial there, which, if supported with results similar to those already received with the recent phase 2 trial with a 25mg dose, should lead to drug approval.
ANP is also pursuing FDA IND. Communications between the company and the FDA seem very positive.

DMD has no real SOC. Drugs used now for DMD do not perform as well as what ATL1102 did in the previous phase 2 trial. ATL1102 was well tolerated with no adverse events reported.
ANP have received ODD (both FDA and EMA) and RPDD with the FDA.

As an investor you need to keep your eye on the prize. Following the DMD pathway, and then prioritizing EMA approval is the quickest and least costly way of getting ATL1102 to market. As a shareholder this means less dilution, and the quickest way for the company to add value to its market cap. Once EMA approval is achieved, and a revenue source is achieved, both ATL1102 and ATL1103 can then be investigated for other indications, providing company future growth. This is the prize!

The share price now is 4 bags higher than Apr last year, and 2 bags higher from where we were this time last year. We should have news from EMA within 6 weeks or so. The market cap today is still under $aud 100 million. Long term holders are up 7 to 10 bags today.

Its important not to be distracted by noise.