Executive Summary
Augment Therapeutics is an early-stage pharmaceutical research and development company, and its mission is to “Leveraging Off-Patent Medicines” and strives to invent “Enhanced” versions of many widely used existing generic drugs that suffer from significant drawbacks or limitations, using our proprietary novel linker/prodrug technologies — including our BINARS™ (Built-In Nucleophile-Assisted Release System) self-immolative linker platform. In the process, we have invented the below mentioned “Enhanced” versions of widely used existing drugs such as naproxen, aspirin, and irinotecan. We strongly believe that these “Enhanced Medicines or E-Medicines”, due to their competitively advantageous properties over their respective parent drugs, are ideal candidates for development through USFDA’s efficient 505(b)(2) regulatory route, which is the least expensive and shortest route to drug development and approval with significantly reduced clinical trial requirements compared to a full NDA.
THE COMPANY AND TEAM
Augment Therapeutics is headquartered in Lake Forest, California, USA and in Hyderabad, Telangana State, India. The co-founders of the US Entity are Dr. Apparao Satyam, PhD (US Citizen), D. Larry Kauvar, PhD (US Citizen), Dr. Vidyasagar Vuligonda, PhD (US Citizen) and Dr. Somesh Sharma, PhD (US Citizen). The co-founders/shareholders of the Indian Entity are Mrs. Veeraveni Baddireddi (Indian citizen & Co-founder) and Dr. Apparao Satyam, PhD (US citizen, OCI & Co-founder), A PhD Pharmacologist (Indian Citizen & Shareholder), A Clinical Research Physician, MD (Indian Citizen & Shareholder) and Mr. Harmeet Singh Lamba, PGD (IIFT) (Indian Citizen & Shareholder).
Augment Scientific Team – Responsible for chemistry, preclinical and clinical research work
Dr. Apparao Satyam, PhD (US Citizen & OCI)
CEO, CSO and Co-founder of both the entities of Augment Therapeutics
35+ Years of drug discovery experience in both Indian and US Pharma industries
Sole inventor of our lead assets and BINARS™ platform
Dr. Vidyasagar Vuligonda (US citizen)
35+ years of experience in small molecule drug design and product development
Confidential Team Members:
PhD Pharmacologist (Indian Citizen)
20+ Years of experience in preclinical research
Clinical Research Physician, MD (Indian Citizen)
20+ Years of experience in clinical research
Augment Scientific Team – Responsible for dealings with US FDA on regulatory affairs
Dr. Somesh Sharma, PhD (US citizen)
40+ Years of drug discovery experience in both Indian and US Pharma industry
Dr. Larry Kauvar, PhD (US citizen)
40+ Years of drug discovery experience in US Pharma industry
Mr. Harmeet Singh Lamba, B. Pharm (BITS, Pilani), PGD (IIFT) (Indian Citizen)
Business Development.
Administrative Team –
Responsible for managing Admin & Finance Departments
Mrs. Veeraveni Baddireddi, MMS (Finance) (Indian Citizen Woman)
Co-founder & Managing Director at Augment Therapeutics Pvt Ltd (INDIA)
Auditor: Mrs. Radhika Vunnam,
Chartered Accountant, Hyderabad, India
Main/Primary Project:
AT-005 (E-Irinotecan) — Discovery of a novel water-soluble prodrug of SN-38 as an “Enhanced Irinotecan” or “E-Irinotecan”.
Irinotecan (Camptosar) is in the WHO List of Essential Medicines and is used for treating metastatic colorectal cancer [either alone or in combination with capecitabine or fluorouracil (5-FU) and leucovorin] and small cell lung cancer (with cisplatin). Irinotecan is also used in combination with folinic acid to treat pancreatic cancers. Despite $9.2B in annual global sales, irinotecan has two distinct, unresolved Pharmacological flaws that have persisted for over 30 years, and no approved Drug has ever fixed those flaws.
The following are Irinotecan’s Two distinct, hitherto unresolved flaws:
Flaw 1 — Grossly Inefficient and Unpredictable Bioactivation: Irinotecan is itself a water-soluble prodrug of SN-38, a highly potent camptothecin analog, but only 2-8% of each administered dose ever converts to active SN-38 in vivo in humans. This Inefficiency is because SN-38 release from irinotecan depends on limitedly available hepatic carboxylesterase enzymes (CES1/CES2), resulting in suboptimal, highly variable tumor drug exposure across patients.
Flaw 2 — Highly Variable SN-38 clearance Causing Severe Toxicities: The SN-38 that is formed is cleared through UGT1A1-mediated glucuronidation, a process that varies dramatically across patients due to UGT1A1 genetic polymorphisms. Patients with reduced uGT1A1 activity accumulate SN-38 systemically, causing severe, life-threatening toxicities including Grade 3–4 diarrhoea and neutropenia — occurring in more than 30% of patients even with current UGT1A1 pharmacogenomic dose optimization, and forming the basis of irinotecan’s FDA Black Box Warning.
The unpredictability of flaw 1 compounds the unpredictability of Flaw 2, making genuinely actionable precision dosing impossible with irinotecan in its current form.
To overcome Flaw 1, we have discovered an “Enhanced Irinotecan” or “E-Irinotecan” or “AT-005”, a new water-soluble prodrug of SN-38, using our proprietary BINARS™ (Built-In nucleophile-Assisted Release System) self-immolative linker, which is pre-oriented for spontaneous intramolecular cyclization at physiological pH (7.4) to release SN-38. In our in vitro drug release study, AT-005 released 100% of SN-38 in human plasma within 15 minutes under physiologically relevant conditions (pH 7.4, 37°C). Hence, our E-Irinotecan (AT-005) does not depend on liver carboxylesterases to release SN-38.
High Potential for UGT1A1-Genotype-Guided Precision Dosing: Critically, because AT-005 controls only the SN-38 release step and does not alter how SN-38 is cleared, this eliminates Flaw 1 entirely and turns UGT1A1 genotype into the sole remaining pharmacokinetic variable. UGT1A1 genotyping is already an FDA-approved test, and is therefore immediately actionable — enabling, for the first time, genuinely actionable, UGT1A1-genotype-guided precision dosing for an irinotecan-equivalent therapy.
It is well established in the published clinical literature on irinotecan itself that plasma AUC of irinotecan and SN-38 increase proportionally with administered dose, that SN-38 levels achieved in humans are roughly 100-fold lower than corresponding irinotecan levels (though highly significant, since SN-38 is 100- to 1,000-fold more cytotoxic than irinotecan), and that irinotecan/SN-38 AUC correlates with leuko-neutropenia and diarrhoea severity. These published PK-PD relationships, established for irinotecan, underscore why better control of SN-38 exposure matters clinically. To be clear, we have not determined or reported AUC data comparing AT-005 to irinotecan; our own preclinical data to date consists of the single-timepoint plasma SN-38 comparison at 2 minutes post-IV dosing in mice described above, together with the in vitro human plasma release data. Generating a full AUC comparison between AT-005 and irinotecan is part of our planned preclinical program.
Since our E-Irinotecan (AT-005) releases SN-38 quantitatively at physiological pH (7.4) and does not depend on any bio-enzymes for its conversion, it eliminates the off-target, irinotecan-specific toxicities (such as acute cholinergic effects) that arise from the intact parent drug itself. This means clinical dose optimization for e-Irinotecan (AT-005) needs to account only for the well-characterized toxicities associated with SN-38 exposure — the same toxicities that current UGT1A1 pharmacogenomic testing is already designed to help manage — rather than the additional, unpredictable layer of variability that irinotecan’s own inefficient activation introduces today.
Although both Irinotecan and e-Irinotecan are water-soluble prodrugs of SN-38 and possess a stable tert-urethane linkage, they release SN-38 to a different extent, as confirmed in the following in vitro and in vivo studies:
In vitro Study: In human plasma at physiologically relevant conditions (pH 7.4, 37°C), E-Irinotecan (AT-005) released 100% of SN-38 within 15 minutes, whereas irinotecan did not release any detectable amount of SN-38 even after 2 hours of incubation — confirming that, unlike Irinotecan, SN-38 release from AT-005 does not depend on carboxylesterase enzymes.
In vivo (PK) Study: when equimolar amounts of both the prodrugs were administered to mice via iv, irinotecan released about 1200 ng/ml of SN-38, whereas E-Irinotecan released nearly double the amount (i.e., 2500 ng/ml) of SN-38 in vivo. this result is not surprising as rodents possess higher amounts of liver carboxylesterases and humans possess only limited amount of liver carboxylesterases; since rodent carboxylesterase activity is reported to be 10-100× higher than in humans, the human clinical advantage of AT-005 over irinotecan is projected to be substantially greater than what is observed in mice.
Competitive Landscape: AT-005 stands apart from other attempts to improve on irinotecan. Onivyde® (Ipsen), a liposomal irinotecan, still inherits irinotecan’s underlying carboxylesterase-dependent activation flaw. Trodelvy® (Gilead), an SN-38 antibody-drug conjugate, achieves near-complete SN-38 payload delivery but relies on an unstable carbonate linker [half-life (t1/2): ~20 hours] prone to premature payload release in systemic circulation — a design limitation we believe likely contributes to Trodelvy®‘s own FDA Boxed Warning for neutropenia and Diarrhea. AT-005’s BINARS™ platform is a 3-in-1 (or a 4-in-1) asset: a standalone enzyme-independent SN-38 prodrug replacing irinotecan, with potential next-generation application as a more stable payload for liposomal formulations, small molecule drug conjugates (SMDCs), and/or antibody-drug conjugates (ADCs).
Based on the above results,
Can <10-20% dose of e-Irinotecan (AT-005) be therapeutically equivalent to the full dose of irinotecan?
Can use of such lower doses of e-Irinotecan (AT-005) have the potential to reduce the intensity of SN-38-associated major side effects such as diarrhoea and neutropenia?
We don’t know answers yet!
However, we are planning to conduct a few relevant in vitro and in vivo preclinical (and eventually clinical) studies to find answers.
High potential for reducing SN-38-induced toxicities via metronomic dosing regimen: Since AT-005 releases 100% of SN-38 in human plasma within 15 minutes, we see potential for a metronomic dosing regimen — frequent, lower-dose administration — to maintain plasma SN-38 levels within a sub-toxic, therapeutic window over a longer period, which could potentially reduce the extent of life-threatening toxicities such as neutropenia and diarrhoea associated with high peak SN-38 exposure. This is a hypothesis we intend to test, and we are planning to design and conduct the relevant preclinical studies in suitable animal models to evaluate it.
IP/Patent Status: A non-provisional patent application covering AT-005 and the BINARS™ linker platform was filed with the Indian Patent Office on 9th July 2026. Accelerated examination has been requested as a DPIIT-recognized Indian Startup under the startup India SIPP Scheme. Corresponding PCT and US National Phase applications are planned.
Additional/Ancillary Projects:
Beyond our primary oncology asset AT-005 (built on our BINARS™ self-immolative linker platform), we have also developed two additional, earlier-stage “Enhanced Medicines” using a separate, novel acid-labile linker technology, described below.
Additional Project A: AT-002 (E-Naproxen) — Development of NO-Naproxen as an “Enhanced” version of the widely used pain and arthritis medicine naproxen through the 505(b)(2) regulatory route.
Generic naproxen, a non-steroidal anti-inflammatory drug (NSAID), is widely used for the treatment of pain and other inflammatory conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, gout, menstrual cramps, etc. However, like most other NSAIDs, long-term use of naproxen is associated with severe 
gastrointestinal (GI) lesions, ulcers, and bleeding. Additionally, recent studies have shown an increased risk of major cardiovascular events such as rise in blood pressure within 30 days of an NSAID use. To reduce the NSAID-induced GI complications, a few approaches such as co-medication with acid suppressants such as proton pump inhibitors (PPIs) and prostaglandin analogues are currently used. However, long term use of PPIs has shown many side effects. In the mid-1990s, COX-2 selective inhibitors were introduced as gastro-protective NSAIDs, and they became very successful within a short period of time. However, some of these COX-2 inhibitors were withdrawn from market due to their inherent cardiovascular risk. This has created a real unmet medical need for safer versions of NSAIDs which do not cause the said GI complications. Recently, a new class of nitric oxide (NO) releasing prodrugs of NSAIDs or simply NO-NSAIDs, are being studied as potentially gastro-protective NSAIDs. These NO-NSAIDs mostly retain the anti-inflammatory properties of parent NSAID, but they also exhibit significantly reduced GI toxicity, which is attributable to the beneficial effects of NO released from these compounds.
We have now discovered a novel NO-Naproxen prodrug (2A/P7133/AT-002), which is aptly named as “Enhanced Naproxen” or “E-Naproxen”, by using a novel platform linker technology and our E-Naproxen:
- Exhibited statistically significant superior bioavailability than naproxen in rats [See Figure 6 showing comparison of bioavailability data among naproxen and its prodrugs 2A (P7133/AT-002), 2B (P7135), 2C (P7134) and 2D (P7132)];
- Protected experimental rats from NSAID-induced gastric damage, which could be due to the beneficial effects of NO released from this NO-NSAID (See Figures S2 and 9).
- May show anti-hypertensive potential due to release of NO, which is a known vasodilator and regulator of blood pressure.
Thus, as shown in Figure 6, our E-Naproxen (2A/AT-002) has exhibited statistically significant increase in bioavailability (AUC: 272.60 ± 8.50 mg*h/ml, **p <0.01 vs naproxen) over its parent drug naproxen [AUC: 207.80 ± 18.20 mg*h/ ml, **p <0.01 vs NO-Naproxen (2A/AT-002)]. To our knowledge, this is the first report of a naproxen prodrug having a statistically significant increase in bioavailability than its parent drug naproxen.
Interestingly, as shown in Figure 6, our E-Naproxen (2A/AT-002) has exhibited a more controlled or sustained release of naproxen and maintained a higher plasma drug concentration over a longer period (>30 micrograms/ml plasma drug concentration up to 6 hrs. duration) when compared to that of naproxen at equimolar doses. Our E-Naproxen is therefore expected to offer better pain relief over a longer period than the parent drug naproxen.
Figure S2. Images of rat stomachs showing gastric lesion and ulcer induction/sparing following acute oral administration of naproxen sodium (109.52 mg/kg, which is equimolar to 100 mg/kg dose of naproxen) and its promising NO-naproxen prodrug 2A (I-D2-R1 or P7133 or AT-002) at 138.67 mg/kg, which is a dose equimolar to 100 mg/kg dose of naproxen in rats.
Strong Possibility for Drug Development and Approval through 505(b)(2) NDA route: We strongly believe that our E-Naproxen (P7133/A2/AT-002), with its above-mentioned competitively advantageous properties over naproxen, is an ideal candidate for development through 505(b)(2) regulatory route, which is the least expensive shorter route for drug approval.
The data shown in Figures S2 and 9 clearly demonstrate that the animals treated with E-Naproxen
(2A/AT-002) caused only minimal or negligible gastric lesions. However, severe hemorrhagic lesions and ulcers were developed in rats administered with parent drug naproxen at equimolar doses (i.e., Gastric lesion and ulcer area: 39 ± 20 mm2 for E-Naproxen vs 580 ± 80 mm2 for naproxen; *** p<0.001). We believe that the observed gastric-sparing effects of our promising E-Naproxen (2A/AT-002) could be attributable to gastro-protective properties of NO released from this novel NO-Naproxen.
Competitive Advantages and Market Impact: The above-mentioned positive attributes make the E-Naproxen (P7133/2A/AT-002) competitively advantageous over naproxen. We therefore believe that this E-Naproxen could represent a novel “First-in-the-Class” of “Safer NSAID” for the treatment of arthritic pain and a host of inflammatory diseases. Thus, this E-Naproxen, when it is approved, has the greatest potential to create disruption in NSAIDs market by grabbing significant market share from naproxen and other approved NSAIDs and has the potential to become a BLOCKBUSTER drug within a short period of its introduction to market.
IP/Patents: We have already obtained US, Canadian and Indian patents covering our E-Naproxen [See US 9,844,599, (Dec 19, 2017), CA 2 897 571 C (Dec 18, 2018) and IN 345054 (Aug 25, 2020)]. We have also published this work [See Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5587-92].
Additional Project B: AT-003 (E-Aspirin) — NO-Aspirin as an “Enhanced” version of the widely used wonder drug aspirin:
Aspirin has been in use as an anti-inflammatory and anti-pyretic drug for over 100 years. Recently, aspirin is also widely used for the treatment of cardiovascular diseases. However, significant number of aspirin users suffer from NSAID-induced severe gastrointestinal lesions, bleeding and ulcers. Currently, proton pump inhibitors are used in combination with aspirin to reduce NSAID-induced GI damage. However, long-term use of PPIs leads to many side effects such as osteoporotic fractures. So, there is an immediate unmet medical need for safer versions of aspirin. As a solution, we have now invented an “Enhanced Aspirin” or “E-Aspirin” or “AT-003”, which has shown comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin but it did not cause any significant NSAID-induced gastric lesions, bleeding, and ulcers. Thus, our E-Aspirin (AT-003) represents a First-in-Class of potentially “Safe Aspirin” for the treatment of cardiovascular disorders and is an ideal candidate for development through the least expensive 505(b)(2) regulatory route.
IP/Patents: We have already obtained US, Canadian and Indian patents covering our E-Aspirin [See US 9,844,599, (Dec 19, 2017), CA 2 897 571 C (Dec 18, 2018) and IN 345054 (Aug 25, 2020)]. We have also published this work [See Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5587-92].
Exclusive Licensing of Proprietary Novel Linker Technologies: An exclusive license agreement to the technology has been secured from Piramal Enterprises, Mumbai, India.
For further Information, please contact:
Dr. Apparao Satyam, PhD.
CEO & CSO, Augment Therapeutics
The US Entity: Lake Forest, CA 92630, USA
The Indian Entity: Hyderabad-500089, India
Tel: +91-9502043658 (WhatsApp: 9502043658)
Email: apparao.satyam@augmenttherapeutics.com
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