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TLC Corporate PresentationConfidential Legal disclaimers 2 This presentation contains forward...
Transcript of TLC Corporate PresentationConfidential Legal disclaimers 2 This presentation contains forward...
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TLC Corporate Presentation George Yeh President
Confidential
Legal disclaimers
2
This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by the words “will,” “expect,” “intend,” “plan,” “objective,” “believe,” “estimate,” “potential,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. These statements are based on management’s current beliefs and expectations. These statements include but are not limited to statements regarding our business strategy, our plans to develop and commercialize our product candidates, our plans to enter into transactions with commercial or strategic partners, the safety and efficacy of our product candidates, our expectations regarding timing, design and results of clinical trials of our product candidates, our plans and expected timing with respect to regulatory filings and approvals, the size and growth potential of the markets for our product candidates, and our ability to serve those markets, and our plans and expected timing with respect to regulatory filings and approvals. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Factors that may cause our actual results to vary from current expectations are discussed in our prospectus relating to our initial public offering and our other filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections therein. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation.
The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.
Confidential
Investment highlight TLC is well-positioned to fulfill unmet medical needs
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Experienced & dedicated team CEO’s 3rd liposome company following 2 drug approvals; President’s 2nd Seasoned management team with big pharma background ~120 employees (4 MDs, 40PhDs) with liposomal science expertise
LipAD® Lipid-Assembled Drug Delivery platforms BioSeizer® sustained release NanoX™ tissue-targeted delivery, proven in 2 approved drugs
Diverse late-stage pipeline featuring known APIs
Pain (TLC599 & TLC590) / ophthalmology (TLC399) / oncology (TLC178) 505(b)(2) regulatory pathway for expedited approval
Strong global IP protection Wholly owned product candidates & technology platforms 199 patents worldwide - 122 issued / 77 applications
Public company with distinguished reputation Dual-listed on Nasdaq (TLC) & Taipei Exchange (4152) Ranked top 5% every year in corporate governance evaluation
Confidential
Keelung Hong, PhD Founder, Chairman, CEO
35+ years liposomal science experience NanoX™ & Onivyde co-inventor
George Yeh, MBA President
20+ years in biotech/finance Hermes Biosciences CFO MOEA National Industrial Innovation Award winner
George Spencer-Green, MD Chief Medical Officer
35+ years experience Pfizer VP & clinical head Humira registration & extension clinical lead
Nicole Lin, MBA Chief Financial Officer
28+ years finance/accounting experience
Wenji Chen, PhD, MBA VP, Corporate Development
26+ years business/research development experience
Vincent Chang, PhD VP, Manufacturing
35+ years biotech & CMC consulting experience 11+ years at Abbott
Yunlong Tseng, PhD VP, Research & Development
20+ years chemistry & R&D experience NanoX™ co-inventor
Sheue Fang Shih Head of Product Development
20+ years protein drug delivery & targeted delivery experience BioSeizer® inventor
Experienced & dedicated management team with extensive drug development know-how
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Confidential
Targeted Delivery
More options for payload selection
Efficient particle size for enhanced delivery
Reduced dose frequency
Robust, scalable & replicable manufacturing
Applicable to our library of 80+ compounds
Lipid-based drug delivery platforms designed to create innovative products
TLC599
TLC399
2011 Pacira
Exparel
2015 FDA Liposome Guidance
Sustained Release
TLC590 Controlled release
from days to months Can deliver biologics
or small molecules Fully biodegradable
components Economical
manufacturing process
Scale-up capabilities
1995 Sequus/Alza/J&J
Doxil 2015
Hermes/Merrimack/Ipsen Onivyde
TLC178
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BioSeizer®
NanoX™
Confidential
A robust pipeline
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Program Preclinical Phase I Phase II Phase III Anticipated Milestones
Pain Management
TLC599 Last patient enrollment
2H2020
TLC590 Last patient enrollment
1H2020
Ophthalmology
TLC399 Last patient enrolment 1H2020
Oncology
TLC178 Ph I/II MTD Q4W 2H2019
Adult advanced malignancies/ STS1
Osteoarthritis pain
Macular edema
Post-op pain
1 Soft tissue sarcoma (STS); Orphan Drug Designation (ODD) 2 Pediatric rhabdomyosarcoma (RMS); designated Drug for Rare Pediatric Disease (RPD)
Pediatric RMS2
TM
Osteoarthritis (OA) Pain Program TLC599: BioSeizer® sustained release dexamethasone sodium phosphate (DSP) intraarticular injection for OA pain
Confidential
Current treatment landscape
TLC599
TLC599 target product profile Fast acting, long lasting, low toxicity non-opioid intraarticular injection for OA
Our strategic solution: TLC599
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1 Arthritis Foundation. Arthritis By the Numbers / Book of Trusted Facts & Figures. 2 National Institutes of Health. FACT SHEET – Osteoarthritis., 2010 3
Intra-articular steroid injections for painful knees. Can Fam Physician 2004;50:241-248. 4 State-of-the-Art management of knee osteoarthritis. World J Clin Cases 2015; 3(2): 89-101. 5 The chondrotoxicity of single-dose corticosteroids. Knee Surg Sports Traumatol Arthrosc. 2012 Sep;20(9):1809-14.
30.8 million OA patients in US1;20% of people >65 years at risk for OA by 20302
Efficacy of viscosupplements / hyaluronic acid (HA) is “inconclusive”
Triamcinolone acetonide (TA) may be chondrotoxic
Opioids are highly addictive
Target for 6-month efficacy Phase II data showed significantly better pain reduction than placebo through 6 months
Minimized cartilage damage & toxicity Preclinical & Phase II MRI data indicated potential chondroprotection
Improved drug retention in joint Contrived formulation & particle size ~400nm
Needle gauge flexibility for future expanded indications into small joints
Confidential
Features comparison Current data for TLC599 vs other treatments
Product Attributes IR Steroid ER Steroid TLC599
Sustained release formulation ✗ ✓ ✓ Pain management up to 6 months ✗ ✗ ✓ Safer API & minimal damage to cartilage1 2 ✗ ✗ ✓ Better systemic safety with drug retention in joint ✗ ✓ ✓ Possible indication expansion into smaller joint space ✓ ✗ ✓ Easy to use one-vial application ✓ ✗ ✓ No need for wholly aseptic manufacturing process3 ✓ ✗ ✓
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1 Intra-articular injections for osteoarthritis of the knee. Cleveland Clinic Journal of Medicine, vol. 73, No. 10, Oct 2006. 897-911. 2 Extreme Post-injection Flare in Response to Intra-Articular Triamcinolone Acetonide (Kenalog), The American Journal of Orthopedics Mar/Apr 2016. 108-111. 3 “Flexion sets up house with Patheon to make its pain drug”, Chemical & Engineering News. April 4, 2016.
Confidential
Preclinical in vivo TK study TLC599 demonstrated minimal systemic exposure
TLC599 was intraarticularly injected into dog knee joints (n=8). Synovial fluid and plasma were collected for DSP concentration analysis. LLOQ=40ng/mL
Dog TK Study
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Plasma
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Preclinical in vivo PK study TLC599 demonstrated sustained drug levels in the joint space for 120 days
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TLC599 was intraarticularly injected into dog knee joints (n=4). Synovial fluid was collected for DSP concentration analysis. LLOQ=2750pg/mL
Dog PK Study
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Preclinical chondrotoxicity study in dogs and rabbits TLC599 showed no cartilage toxicity after single/multiple doses or against TA
TA = triamcinolone acetonide / ER TA = extended release triamcinolone acetonide 12
Saline
TA 2.1mg
TA 18.75mg
TLC599 12mg (eq. to 60mg TA)
ER TA 2.1mg
ER TA 18.75mg
Synovial TK study (Dogs, Day 30): No marked cartilage toxicity in TLC599 Proteoglycan loss in TA & ER TA 2.1mg ER TA showed more damage
than 2.1mg TA
No intensity or morphology change observed; neither proteoglycan loss nor cartilage damage even after repeat dosing.
TLC599 Single Dose Dog, 12mg (eq. to 60mg TA)
A1, Day 8
A2, Day 31 B2, Day 31
B3, Day 91 A3, Day 91
TLC599 Repeat Dose Rabbit, 1.2mg (eq. to 6mg TA)
B1, Day 15
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TLC599 Phase II clinical trial Phase II trial design & demographics
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Placebo (saline)
IA injection (n=25)
TLC599 12mg
IA injection (n=26)
TLC599 18mg
IA injection (n=24)
Age Average
≥66
64.8 (8.45) 11 (44.0%)
63.9 (9.07) 10 (38.5%)
62.9 (8.80) 9 (37.5%)
Gender Male
Female
28% 72%
42.3% 57.7%
29.2% 70.8%
Race Asian
Caucasian
12 (48.0%) 13 (52.0%)
13 (50.0%) 13 (50.0%)
12 (50.0%) 11 (45.8%)
Knee OA Unilateral Bilateral
40% 60%
38.5% 61.5%
38.7% 61.3%
K-L Grade 2 3
36% 64%
50% 50%
37.5% 62.5%
TLC599 12mg met the primary endpoint, with significant reductions in WOMAC pain (p=0.0027) through 12 weeks
Both doses of TLC599 resulted in greater reductions in pain than placebo
Data from 12mg presented as optimal dose
Confidential
0
10
20
30
40
50
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W12 W16 W20 W24
Perc
enta
ge (
%)
of D
urab
le
Res
pond
ers
-5.0
-4.5
-4.0
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
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0 4 8 12 16 20 24
LS M
ean
Cha
nge
from
BL
Week
Placebo (n=25)
TLC599 12mg (n=26)
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0 4 8 12 16 20 24
LS M
ean
Cha
nge
from
BL
Week
Phase II clinical trial: pain reduction TLC599 showed statistical significance against placebo at every scheduled visit
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* * * *
* * *
WOMAC Pain (0-4)
VAS Pain (0-10)
* * * * *
* *
* Statistical significance p-values from Mixed Effect Model Repeated Measure, LS mean change from baseline of WOMAC/VAS Pain vs Placebo
WOMAC ≥30% Durable Response
TLC599 showed statistical significance against placebo at every scheduled visit in WOMAC Pain, VAS Pain & Durable Response
WOMAC Function & WOMAC Stiffness also showed same pain reduction pattern
* Statistical significance Pain score reduction of ≥30% = clinically important difference p-values from Logistic regression model of WOMAC pain vs Placebo
* * * *
Confidential
50% patients did not take any acetaminophen during the first 12wks in TLC599 12mg group
After 12wks, median acetaminophen consumption in placebo group was 5-8 times that of TLC599 12mg group
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Phase II clinical trial: rescue medication use Less acetaminophen consumption at everyone time point
Confidential
Phase II clinical trial: safety profile – AEs TLC599 was well tolerated, with comparable frequency of TEAEs to placebo
Placebo n=25
TLC599 12mg n=26
TLC599 18mg n=24
TEAE 17 (68%) 18 (69.2%) 20 (83.3%)
Treatment-related TEAE 4 (16%) 7 (26.9%) 11 (45.8%)
Treatment-related SAE 0 0 0
Index knee-related TEAE 4 (16%) 1 (3.8%) 3 (12.5%)
TEAE related to injection procedure 3 (12%) 1 (3.8%) 3 (12.5%)
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Treatment-emergent adverse events (TEAEs) among the three groups (TLC599 12mg, TLC599 18mg and placebo) were comparable
No life-threatening treatment-related TEAE; no unexpected safety signals No deaths, no treatment related serious adverse events (SAEs)
Confidential
Phase II clinical trial: safety profile – knee MRI TLC599 demonstrated protection / delay in cartilage degeneration
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Articular cartilage deterioration was assessed using semi-quantitative magnetic resonance imaging (MRI) Osteoarthritis Knee Scoring (MOAKS) instrument
Two categorical MOAKS scores 14 sub-regions of knee joints (1) the size of cartilage damage (2) the depth of cartilage damage
-9%
-15%
-4%
-8%
9%
0%
-20% -15% -10% -5% 0% 5% 10% 15% 20%
TLC599 (18 mg) (Full thickness loss)
TLC599 (18 mg) (Surface area loss)
TLC599 (12 mg) (Full thickness loss)
TLC599 (12 mg) (Surface area loss)
Placebo (Full thickness loss)
Placebo (Surface area loss)
Favorable Unfavorable
Absolute difference of 6M cartilage deterioration rate (Study knee minus Non-study knee)
Confidential
TLC599 key findings presented by PI and Winner of OARSI Clinical Research Award
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- Dr. David Hunter Professor of Medicine, University of Sydney
Winner of 2019 OARSI Clinical Research Award Principal investigator, TLC599 Phase II trial
“I am impressed with TLC599’s ability to consistently provide fast and durable pain relief in the majority of patients for the entire follow-up period of six months.”
Oral Presentation by Dr. David Hunter: Single Intraarticular Injection of TLC599 Provided Sustained Pain Relief through 24 Weeks in Participants with Symptomatic Knee Osteoarthritis Statistically significant WOMAC & VAS Pain reduction through Week 12, 16, 20, 24 Statistically significant WOMAC & VAS Pain at Week 1, 4, 8, 12, 16, 20, 24 Similar results in WOMAC Function Statistically significant WOMAC & VAS Pain durable response (maintain >30% reduction)
in over half of subjects, indicating clinically meaningful pain relief Greatly reduced acetaminophen consumption Most adverse events were mild to moderate
Confidential 19
Multi-center, randomized, double-blind, placebo- and active comparator-controlled Phase III pivotal study
40-50 sites in the US and Australia Evaluation of safety and efficacy of single and repeated doses in ~500 knee
OA patients (KL Grade 2-3)
Primary endpoint: ◦ Change from BL in WOMAC pain vs placebo at Week 16 / Week 40
Key secondary endpoints: ◦ Change from BL in WOMAC Pain/Function vs placebo/DSP at Weeks 16, 20,
24, through 52 weeks, PGIC
Phase III pivotal clinical trial “EXCELLENCE” global trial design
Rand 2:1:1
BL 24 52
First injection Second injection
TLC599
DSP TLC599
Placebo Placebo
TLC599
500 patients will be randomized in 2:1:1 ratio treated with TLC599, DSP or placebo
Patients will receive a second blinded injection at Week 24
20 16 40 4 8 12 44 28 32 36 48 1 2 Study weeks
Confidential
Market research study with 16-week pain control TLC599 could achieve usage in 26% of all US knee OA patients
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4mo sustained pain relief
Fast pain relief as
quickly as
1wk
Better WOMAC Pain
Reduction
Safer for repeat
dosing
21G-30G
needle size
TLC599 Optimal Profile
Source: ZS Associates Market Study
Payers estimate 4-month efficacy of TLC599 profile might achieve price of $627-$684
TM
Post-Surgical Pain Program TLC590: BioSeizer® sustained release ropivacaine injection for post-operative pain management
Confidential
TLC590 target product profile Fast acting, long lasting non-opioid post-operative local anesthetic
96 million surgical procedures performed in the US in 20121
Local anesthetics play a major role in the management of post-surgical pain2 Long acting agents have modestly expanded duration, but API in current marketed
liposomal formulation of bupivacaine has higher toxicities3
Current local anesthetic landscape
Target for 4-7 days duration with immediate onset Supported by data from Phase I/II trial in hernia repair
Unchanged clinical practice during post-op surgery Same administration as current standard of care products
Potential for lower COGS allows for monetization of hospital opportunity
Our strategic solution: TLC590
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1 World Bank. Number of surgical Procedures. 2 Infiltration of Local Anesthetics for Postoperative Analgesia. Pfiedler Enterprises. 2015. 3 Local Anesthetics Systemic Toxicity Association with Exparel (Bupivacaine Liposome)- A Pharmacovigilance evaluation, Expert Opinion on Drug Safety. Expert Opin Drug Saf. 2017 Jun 5:1-7
Confidential
Features comparison Current data for TLC590 vs other postsurgical pain management drugs
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1 2 Local Anesthetics Systemic Toxicity Association with Exparel (Bupivacaine Liposome)- A Pharmacovigilance evaluation, Expert Opinion on Drug Safety. Expert Opin Drug Saf. 2017 Jun 5:1-7 3 Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia. Journal of Pain Research 2012:5 107–116 4 Phase 2 studies of HTX-011 in the management of post-operative pain. Aug 1, 2016. 5 Guidance for Industry. Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice. 2004
Product Attributes Generic Local
Anesthetics
ER Bupivacaine
ER Bupivacaine + Meloxicam
TLC590 (ER
Ropivacaine)
Sustained release formulation ✗ ✓ ✓ ✓ Lower Local anesthetic systemic toxicity (LAST) – cardiovascular1 ✗ ✗ ✗ ✓ Lower LAST – central nervous system2 ✗ ✗ ✗ ✓ Pain management up to 168 hours34 ✗ ✗ ✗ ✓ Near-end stage sterile filtration only – no need for wholly aseptic manufacturing process5
✓ ✗ ✗ ✓ Lower risk of foreign particulate ✓ ✗ ✗ ✓
Confidential
Preclinical rat PK study TLC590 half-life after subcutaneous injection is significantly prolonged compared to IR ropivacaine
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L)
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IR ropivacaine 19mg (n=6)
TLC590 114mg (n=6)
Confidential
Preclinical paw incision analgesic study TLC590 produced statistically significant reductions in pain compared to ER bupivacaine
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In TLC590 displayed… Statistically significant
reductions in pain at 0.5, 5, & 6 hours post-injection compared to ER bupivacaine at equipotent dose
Earlier onset & longer analgesic action than ER bupivacaine
Longer analgesic action than free ropivacaine
*
*
*
Confidential
Preclinical nerve block study TLC590 exhibited more robust magnitude & duration of analgesia
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TLC590 exhibited larger magnitude of analgesia which persisted to the 9th hour
Analgesic action of ER bupivacaine diminished & was comparable to saline by the 8th hour
Confidential
Phase I/II clinical trial in inguinal hernia repair surgery Study design & demographics
27 Confidential
Ropiva- caine
150 mg (n=16)
TLC590 190 mg (n=12)
TLC590 380 mg (n=12)
TLC590 475 mg (n=12)
TLC590 570 mg (n=12)
Age (years)
Mean (SD) 42.8 (13.68)
50.8 (9.11)
46.5 (13.45)
50.0 (13.05)
44.7 (15.74)
Median 43.5 55.0 50.0 56.0 48.0 Min, Max 20, 64 33, 60 20, 62 25, 62 23, 63
Gender, n (%) Male 15 (93.8) 12 (100) 11 (91.7) 10 (83.3) 12 (100)
Female 1 ( 6.3) 0 1 ( 8.3) 2 (16.7) 0 Race, n (%)
Asian 0 0 0 0 0 White 16 (100) 11 (91.7) 12 (100) 12 (100) 12 (100)
American Indian or Alaska
Native/White 0 1 ( 8.3) 0 0 0
Ethnicity, n (%) Hispanic or
Latino 1 ( 6.3) 0 0 0 0
Not Hispanic or Latino 15 (93.8) 12 (100) 12 (100) 12 (100) 12 (100)
TLC590 475mg significantly reduced pain (AUC0-96h p=0.0103)
All four doses resulted great reductions than ropivacaine
Data from 475mg presented as optimal dose
Confidential
Phase I/II clinical trial in inguinal hernia repair surgery TLC590 pharmacokinetics profile
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TLC590 475mg
TLC590 380mg
TLC590 190mg
Ropivacaine 150mg
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Confidential
Phase I/II clinical trial – inguinal hernia repair surgery TLC590 exhibited highly dose-linear pharmacokinetics in Cmax & AUC
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R² = 0.9093
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ine
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mL)
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AUC
Confidential
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TLC590 475 mg (n=12)
Incr
easi
ng p
ain
Severe pain
AUC0-24 p=0.0057
AUC0-48 p=0.0131
AUC0-72 p=0.0117
AUC0-96 p=0.0103
±
Phase I/II clinical trial – inguinal hernia repair surgery TLC590 reduced pain against ropivacaine through 168 hours
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TLC590 significantly reduced pain through 96 hours Greater reductions in pain than ropivacaine at every 24-hour interval
through 168 hours
Confidential
Phase I/II clinical trial – inguinal hernia repair surgery TLC590 reduced opioid use & improved time to first opioid use
3.3
13.0
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
Ropivacaine TLC590 475mgTi
me
to fi
rst o
pioi
d us
e (m
edia
n hr
s)
Time to First Opioid Use Mean Rescue Opioid Over Time (mg per subject)
31 Confidential
Ropivacaine TLC590 475mg
0 – 24 hrs 78.1 29.2
0 – 48 hrs 115.6 54.2
0 – 72 hrs 118.8 54.2
0 – 96 hrs 118.8 54.2
• 58.3% of patients in the TLC590 475mg group remained opioid-free through the entire duration of the study
• Mean total opioid consumption was 54% less than that of the ropivacaine group through 96 hours post-surgery.
Confidential
Phase I/II clinical trial – inguinal hernia repair surgery TLC590 was well tolerated, no serious or severe adverse events
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Ropivacaine 150mg (n=16)
TLC590 190mg (n=12)
TLC590 380mg (n=12)
TLC590 475mg (n=12)
TLC590 570mg (n=12)
Any TEAE n (%) 13 (81.3) 11 (91.7) 8 (66.7) 10 (83.3) 7 (58.3)
Any Related TEAE n (%)
2 (12.5) 1 (8.3) 2 (16.7) 2 (16.7) 2 (16.7)
Any Serious TEAE 0 0 0 0 0
Subjects with at least one Severe TEAE
0 0 0 0 0
TEAE: treatment-emergent adverse event
Confidential
Phase I/II clinical trial – inguinal hernia repair surgery Topline data
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All four doses of TLC590 resulted in greater reductions in pain than standard ropivacaine as measured by AUC at every interval through 96 hours
TLC590 570mg is not MTD, high dose could apply to other large wound surgeries TLC590 475mg vs standard ropivacaine, extremely durable, statistically significant and
clinically meaningful pain reduction; differences maintained through 1 week • AUC0-24h TLC590 vs ropivacaine, p=0.0057 • AUC0-48h TLC590 vs ropivacaine, p=0.0131 • AUC0-72h TLC590 vs ropivacaine, p=0.0117 • AUC0-96h TLC590 vs ropivacaine, p=0.0103
Reduction of opioid use vs standard ropivacaine • Mean total opioid use reduced 54% through 96hr
• Time to first opioid use was ~4X that of the ropivacaine group (median 13.0 vs 3.3 hrs)
• 58% of opioid-free subjects to the end of study
“These findings, combined with an extremely favorable side-effect profile and the product’s ease of administration, give great cause for optimism that TLC590 will be a formidable non-opioid tool for the treatment of both acute and long-term postsurgical pain in the future.”
- Dr. Todd Bertoch
Principal investigator, TLC590 Phase I/II trial
Confidential
Phase II clinical trial – bunionectomy Design & objectives
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Primary Objective: Evaluate the analgesic efficacy of TLC590 for postsurgical pain management in subjects following
bunionectomy
Secondary Objectives: Evaluate PK profile and dose-exposure relationship and bioavailability compared to free ropivacaine Evaluate safety and tolerability of TLC590 Evaluate the exposure-response relationship between PK parameters and pain intensity
152mg TLC590
n=12
190mg TLC590
n=12
228mg TLC590
n=12
50mg Ropivacaine
n=12
Saline Placebo
50mg Bupivacaine
Part 1: Blinded PK study of TLC590 and ropivacaine (completed)
Part 2: Efficacy and safety of TLC590 vs bupivacaine and placebo
Dose linearity and relative bioavailability of TLC590 established All three doses of TLC590 were well tolerated; safety profile comparable to ropivacaine - Most TEAEs mild to moderate; no TRAEs or SAEs, - No AEs leading to withdrawal TLC590 228mg chosen to move forward based on maximum feasible volume
228mg TLC590
TM
Ophthalmic Disease Program TLC399: BioSeizer® sustained release dexamethasone sodium phosphate (DSP) intravitreal injection for macular edema (ME) due to retinal vein occlusion (RVO)
Confidential
TLC399 target product profile Fast acting, long lasting non-implant dexamethasone intravitreal injection
RVO affects >16 million adults worldwide1
Steroids play prominent role even post advent of anti-VEGF2
Current marketed dexamethasone injection lasts 1-3 months3, but implant takes up to 6 months to dissolve4, and 22G needle causes bleeding in 23% of patients3
Current treatment landscape for RVO
Target for > 6-month duration with immediate onset, supported by preclinical & phase I/II data
Small needle size (30G, no implant) 2.3 times smaller than diameter of current marketed steroid injection, reducing risk of conjunctival hemorrhaging & infections
Our strategic solution: TLC399
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1 Sophie Rogers et al, “The Presence of Retinal Vein Occlusion: Pooled Data from Population Studies from the United States, Europe, Asia and Australia; 117(2): 313-9el. (2010). 2 Effect of intravitreal triamcinolone in diabetic macular edema unresponsive to intravitreal bevacizumab. Jeon S1, Lee WK. Retina. 2014 Aug;34(8):1606-11. 3 Ozurdex® Prescribing Information 4 Ozurdex drug delivery implant for eyes, The Macula Center, Dana M. Deupree, MD, FACS & Michael Tolentino, MD
Approved steroid implant 22G / 0.7176mm
TLC399 (no implant)
30G / 0.3112mm
Confidential
Extending BioSeizer to anti-VEGF Ab: in vivo evidence of much longer duration
Concentration of Anti-VEGF can be significantly maintained from 1-2 months to >4 months when engaged with TLC’s proprietary BioSeizer technology
Effective concentration 0.5ug/ml
Rabbit IVT PK Profile Measured by ELISA
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TM
Soft Tissue Sarcoma Program TLC178: NanoX tumor-concentrated delivery of vinorelbine for rhabdomyosarcoma (RMS) & potentially for soft tissue sarcomas (STS) & non-small cell lung carcinoma (NSCLC)
Confidential
TLC178 target product profile Safer, less toxic, more durable anticancer drug with RPD & ODD designations
Vinorelbine (VNB) + cyclophosphamide combo as therapy agent or VNB alone for palliative therapy1 for RMS, but with significant dose-limiting myelosuppression2 3
Vinorelbine + gemcitabine (Gem) combo as active regimen for STS & NSCLC4 5
Current treatment landscape
Improve selective delivery to tumor versus non-tumor tissue
Higher drug concentration at tumor confers higher activity
Less drug to non-tumor reduces myelosuppression, enabling higher dose intensity
Efficacy improvement in treatment response rate & duration of response
Rare Pediatric Disease Designation (RMS) Orphan Drug Designation (STS)
Our strategic solution: TLC178
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1 National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology – Soft Tissue Sarcoma, Version 1.2018, October 31, 2017. 2 Phase II Evaluation of Intravenous Vinorelbine (Navelbine) in Recurrent or Refractory Pediatric Malignancies: A Children's Oncology Group Study. Pediatric Blood Cancer. 2009 October ; 53(4): 590–93. 3 Vinorelbine in Previously Treated Advanced Childhood Sarcomas .Cancer 2002;94:3263–68. 4 Gemcitabine and Vinorelbine Combination Chemotherapy for Patients With Advanced Soft Tissue Sarcomas. Cancer 2007;109:1863-69. 5 The Novel and Effective Non-platinum, Nontaxane Combination of Gemcitabine and Vinorelbine in Advanced Non-small Cell Lung Carcinoma. Cancer 2002;95(2)340-53.
Confidential
Preclinical studies TLC178 showed significantly better tumor control in in fibrosarcoma, RMS & NSCLC models
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Post drug injection day0 5 10 15 20 25 30
Tum
or vo
lum
e (m
m3 )
0
500
1000
1500
2000Placebo (D5W)Doxorubicin 3.4mg/kgTLC178 5mg/kg
TLC178 showed significant tumor inhibition response vs doxorubicin in fibrosarcoma model
Fibrosarcoma Model
Post drug injection day0 10 20 30 40
Tum
or v
olum
e (m
m3 )
0
500
1000
1500
2000
2500
3000SalineVinorelbine 5mg/kgTLC178 5mg/kg
RMS Model
TLC178 showed significantly better tumor control than free vinorelbine in RMS model
Post first drug injection day
0 2 4 6 8 10 12 14
Tum
or v
olum
e (m
m3 )
0
500
1000
1500
2000
2500Saline5mg/kg VNB5mg/kg TLC1785mg/kg VNB + 25mg/kg Gem5mg/kg TLC178 + 25mg/kg Gem
NSCLC Model
TLC178 showed significantly superior tumor control over VNB & VNB + Gem in NSCLC model
Confidential
Clinical development plan for TLC178 in pRMS with extended indications in STS & NSCLC
Pediatric Rhabdomyosarcoma
Non-Small Cell Lung Cancer (NSCLC) Soft Tissue Sarcoma (STS)
3+3 Dose Escalation
Combo TLC178 + cyclophosphamide
Single-arm (N=40,
ORR/ DoR)
NDA
STS Combo TLC178 +
gemcitabine Single-arm Phase II
(n=100-200)
sNDA
TLC178 alone Phase I/II
MTD
Current status: - 33 patients dosed - MTD (Q4W) found:31mg/m2
- MTD (Q2W) ongoing
NSCLC Combo TLC178 +
gemcitabine Phase II/III adaptive
random
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TM
Milestones
Confidential
Pivotal moments Balanced anticipated short- and long-term milestones
1H2019 2H2019 1H2020 2H2020
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TLC599 Phase III last patient enrollment
TLC590 Pivotal trial initiation (bunionectomy)
TLC590 Pivotal trial initiation (hernia repair) TLC178 Phase I/II initiation (pediatric) after suitable dose found in adults
TLC590 Phase II Part 1 analysis (bunionectomy)
TLC599 Pivotal trial initiation TLC178 Phase I/II MTD Q4W (adult)
TLC599 EOP2 meeting (CMC) TLC599 EOP2 meeting (clinical) TLC590 Phase I/II topline data (hernia repair) TLC178 EU orphan designation
TLC590 Phase II last patient enrollment (bunionectomy) TLC178 Phase I/II data readout (adult) TLC399 Phase II last patient enrollment
2021
TLC599 Pivotal trial topline data
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