Scandion Oncology - Revision history

95.149.241.133 at 16:49, 20 August 2022

2022-08-20T16:49:38Z

← Older revision		Revision as of 17:49, 20 August 2022
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	[[Category:Thesis]]		[[Category:Thesis]]
	[[Category:Equities]]		[[Category:Equities]]

			__INDEX__

>Louis at 16:17, 22 July 2022

2022-07-22T16:17:37Z

← Older revision		Revision as of 17:17, 22 July 2022
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	== References ==		== References ==
			<references />
			[[Category:Thesis]]
			[[Category:Equities]]

>Edison: /* Drug-resistance mechanisms are commonly reported */

2022-06-22T20:56:23Z

Drug-resistance mechanisms are commonly reported

← Older revision		Revision as of 21:56, 22 June 2022
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	== Summary ==		== Summary ==

	'''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which Edison Investment Research expects crucial proof-of-concept results in Q322. The company is also pursuing the Phase Ib PANTAX trial in PC. Assuming proof-of-concept is met, the positioning of SCO-101 in higher lines of mCRC treatment will be essential to maximise value, in Edison Investment Research's view. Edison ~~Investment Research~~ values Scandion Oncology at SEK586.5m or SEK18.3 per share.'''		'''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which Edison Investment Research expects crucial proof-of-concept results in Q322. The company is also pursuing the Phase Ib PANTAX trial in PC. Assuming proof-of-concept is met, the positioning of SCO-101 in higher lines of mCRC treatment will be essential to maximise value, in Edison Investment Research's view. Edison values Scandion Oncology at SEK586.5m or SEK18.3 per share.'''
	{\| class="wikitable"		{\| class="wikitable"
	\|+Key financials summary<ref>Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.</ref>		\|+Key financials summary<ref>Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.</ref>
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	\|Enhanced DNA repair		\|Enhanced DNA repair
	\|Increased activity of nucleotide excision repair system and homologous recombination repair mechanisms.		\|Increased activity of nucleotide excision repair system and homologous recombination repair mechanisms.
	\|		\|Repair of damaged DNA causes increase in tumour cell survival.
	\|		\|Cisplatin, doxorubicin
	\|}		\|}
	In addition to these mechanisms, chemotherapeutic resistance can arise due to alterations to a drug’s target, gene amplifications and epigenetic alterations. Modern approaches to overcoming resistance have focused on developing new, targeted drugs and immunotherapies (for example PD-(L)1 and CTLA4 monoclonal antibodies). However, drug resistance in chemotherapy continues to be recognised as an area of unmet medical need.		In addition to these mechanisms, chemotherapeutic resistance can arise due to alterations to a drug’s target, gene amplifications and epigenetic alterations. Modern approaches to overcoming resistance have focused on developing new, targeted drugs and immunotherapies (for example PD-(L)1 and CTLA4 monoclonal antibodies). However, drug resistance in chemotherapy continues to be recognised as an area of unmet medical need.

>Edison at 15:21, 22 June 2022

2022-06-22T15:21:02Z

← Older revision		Revision as of 16:21, 22 June 2022
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			[[File:Scandion Oncology.jpeg\|thumb]]

			'''Chemotherapy overcoming drug resistance'''

	== Summary ==		== Summary ==

	'''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which Edison Investment Research expects crucial proof-of-concept results in Q322. The company is also pursuing the Phase Ib PANTAX trial in PC. Assuming proof-of-concept is met, the positioning of SCO-101 in higher lines of mCRC treatment will be essential to maximise value, in Edison Investment Research's view. Edison Investment Research values Scandion Oncology at SEK586.5m or SEK18.3 per share.'''		'''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which Edison Investment Research expects crucial proof-of-concept results in Q322. The company is also pursuing the Phase Ib PANTAX trial in PC. Assuming proof-of-concept is met, the positioning of SCO-101 in higher lines of mCRC treatment will be essential to maximise value, in Edison Investment Research's view. Edison Investment Research values Scandion Oncology at SEK586.5m or SEK18.3 per share.'''
	{\| class="wikitable"		{\| class="wikitable"

>Edison at 15:17, 22 June 2022

2022-06-22T15:17:00Z

>Edison: /* Two shots on goal for SCO-101 */

2022-06-22T15:14:38Z

Two shots on goal for SCO-101

← Older revision		Revision as of 16:14, 22 June 2022
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	[[File:Image4-6ff227f569067ae2b29573f4aa4f3314.png]]		[[File:Image4-6ff227f569067ae2b29573f4aa4f3314.png]]



	'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''		'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''

			[[File:Image5-ca177f6ef17ee0c8dfa1ecbf0e399de9.png]]

	The second trial, PANTAX, is a Phase Ib study investigating the safety and tolerability of SCO-101 in patients with unresectable or metastatic PC as an add-on to treatment with nab-paclitaxel and gemcitabine. PC accounts for only 3% of all cancers but 7% of cancer-related deaths, due to the disease’s invasive and often incurable nature. Accordingly, the five-year survival rate for patients with PC is only 11%, dropping to 3% for patients who are diagnosed after the disease has metastasised. The PC treatment market is estimated to reach $5.3bn by 2028 (source: EvaluatePharma). However, Merck’s Keytruda (pembrolizumab) is expected to dominate the market in this period (consensus worldwide sales in 2028 of $2.7bn). Edison Investment Research notes that, as in CRC, many standard PC treatments are off-patent (eg nab-paclitaxel) and if SCO-101 can restore clinical response to these (eg nab-paclitaxel), Edison Investment Research sees an sizable opportunity for Scandion Oncology in this market.		The second trial, PANTAX, is a Phase Ib study investigating the safety and tolerability of SCO-101 in patients with unresectable or metastatic PC as an add-on to treatment with nab-paclitaxel and gemcitabine. PC accounts for only 3% of all cancers but 7% of cancer-related deaths, due to the disease’s invasive and often incurable nature. Accordingly, the five-year survival rate for patients with PC is only 11%, dropping to 3% for patients who are diagnosed after the disease has metastasised. The PC treatment market is estimated to reach $5.3bn by 2028 (source: EvaluatePharma). However, Merck’s Keytruda (pembrolizumab) is expected to dominate the market in this period (consensus worldwide sales in 2028 of $2.7bn). Edison Investment Research notes that, as in CRC, many standard PC treatments are off-patent (eg nab-paclitaxel) and if SCO-101 can restore clinical response to these (eg nab-paclitaxel), Edison Investment Research sees an sizable opportunity for Scandion Oncology in this market.
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	'''Exhibit 5: SCO-101 dual mechanism of action<ref>Source: Scandion Oncology corporate presentation.</ref>'''		'''Exhibit 5: SCO-101 dual mechanism of action<ref>Source: Scandion Oncology corporate presentation.</ref>'''

			[[File:Image6-b18deb263878259b652ac43cea6d3088.png]]

	Additionally, as stated above, SCO-101 inhibits the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) to block the metabolism of chemotherapy drugs and increase systemic levels. The UGT family of enzymes work by modifying a chemotherapy drug with glucuronic acid, therefore making it more water soluble and easier to eliminate from the body. There is a body of clinical evidence that supports the role of UGTs in the development of drug resistance in multiple classes of chemotherapy agents, including alkylating agents, targeted therapies, antiangiogenics and hormonal therapies. Altogether, SCO-101’s dual mechanism acts to reverse drug resistance by increasing the level of chemotherapy drug in the body (through UGT1A1 inhibition) while simultaneously decreasing the ABCG2 mediated removal of the drug from the cell.		Additionally, as stated above, SCO-101 inhibits the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) to block the metabolism of chemotherapy drugs and increase systemic levels. The UGT family of enzymes work by modifying a chemotherapy drug with glucuronic acid, therefore making it more water soluble and easier to eliminate from the body. There is a body of clinical evidence that supports the role of UGTs in the development of drug resistance in multiple classes of chemotherapy agents, including alkylating agents, targeted therapies, antiangiogenics and hormonal therapies. Altogether, SCO-101’s dual mechanism acts to reverse drug resistance by increasing the level of chemotherapy drug in the body (through UGT1A1 inhibition) while simultaneously decreasing the ABCG2 mediated removal of the drug from the cell.
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	First-line therapy for mCRC relies heavily on 5-fluorouracil (5FU)-based chemotherapy regimens, often supplemented with targeted therapies (should a molecular driver be present) and/or biologic agents (eg vascular-endothelial growth factor A, VEGF, targeting monoclonal antibody, bevacizumab). Later lines of therapy will also generally be formed around modification of 5FU-based regimens. A common treatment in this setting is FOLFIRI, a chemotherapy regimen consisting of leucovorin calcium, 5-fluorouracil and irinotecan. One of the active ingredients of this regimen, irinotecan, is a prodrug of the potent topoisomerase I inhibitor SN-38. Drugs of this class kill tumour cells by inhibiting DNA repair processes. The development of resistance to irinotecan chemotherapy through ABCG2 efflux pump overexpression and UTG1A1 activity is well documented, thus Scandion Oncology has identified FOLFIRI as a potentially attractive combination therapy for SCO-101. Indeed, analysis of CORIST patients treated with SCO-101 and irinotecan in Part I of CORIST has shown dramatically increased plasma levels of SN-38 at a 90mg/m2 dose when compared to SN-38 data from treatment with irinotecan at 180 mg/m2 (based on patients outside the CORIST study, Exhibit 6), although Edison Investment Research cautions that there are limitations to comparing data from different studies.		First-line therapy for mCRC relies heavily on 5-fluorouracil (5FU)-based chemotherapy regimens, often supplemented with targeted therapies (should a molecular driver be present) and/or biologic agents (eg vascular-endothelial growth factor A, VEGF, targeting monoclonal antibody, bevacizumab). Later lines of therapy will also generally be formed around modification of 5FU-based regimens. A common treatment in this setting is FOLFIRI, a chemotherapy regimen consisting of leucovorin calcium, 5-fluorouracil and irinotecan. One of the active ingredients of this regimen, irinotecan, is a prodrug of the potent topoisomerase I inhibitor SN-38. Drugs of this class kill tumour cells by inhibiting DNA repair processes. The development of resistance to irinotecan chemotherapy through ABCG2 efflux pump overexpression and UTG1A1 activity is well documented, thus Scandion Oncology has identified FOLFIRI as a potentially attractive combination therapy for SCO-101. Indeed, analysis of CORIST patients treated with SCO-101 and irinotecan in Part I of CORIST has shown dramatically increased plasma levels of SN-38 at a 90mg/m2 dose when compared to SN-38 data from treatment with irinotecan at 180 mg/m2 (based on patients outside the CORIST study, Exhibit 6), although Edison Investment Research cautions that there are limitations to comparing data from different studies.

	'''Exhibit 6: SN-38 plasma concentrations in CORIST patients<ref>Source: Scandion Oncology CMD update.</ref><br />'''		'''Exhibit 6: SN-38 plasma concentrations in CORIST patients<ref>Source: Scandion Oncology CMD update.</ref><br />'''[[File:Image7-c31e427382287da7a43068acd0e06507.png]]

	While plasma concentrations in the CORIST patients were dramatically higher when compared to patients treated only with irinotecan (using data compiled from separate studies), Edison Investment Research notes that high plasma levels of SN-38 do not necessarily correlate with a clinical effect, especially in ABCG2 driven resistance. However, this data does provide support for the SCO-101/FOLFIRI combination with the lower 90mg/m2 CORIST dosing regimen for irinotecan (compared to 180mg/m2 commercial norm).		While plasma concentrations in the CORIST patients were dramatically higher when compared to patients treated only with irinotecan (using data compiled from separate studies), Edison Investment Research notes that high plasma levels of SN-38 do not necessarily correlate with a clinical effect, especially in ABCG2 driven resistance. However, this data does provide support for the SCO-101/FOLFIRI combination with the lower 90mg/m2 CORIST dosing regimen for irinotecan (compared to 180mg/m2 commercial norm).
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	'''Exhibit 7: Preclinical SCO-101 data in combination with paclitaxel'''<ref>Source: Scandion Oncology BACR presentation September 2021.</ref>		'''Exhibit 7: Preclinical SCO-101 data in combination with paclitaxel'''<ref>Source: Scandion Oncology BACR presentation September 2021.</ref>

			[[File:Image8-d2f0ab9ac32701491636345b4497b7bb.png]]
	=== SCO-101 could be first in class in chemotherapy resistance ===		=== SCO-101 could be first in class in chemotherapy resistance ===
	In the past, attention in combatting chemotherapy resistance has focused on repurposing existing therapeutics to serve as add-on treatments to help combat chemotherapy resistance. Specifically, many kinase inhibitors have been investigated as potential combinations to enhance irinotecan response. These include sorafenib, imatinib mesylate, sunitinib, nilotinib and dasatinib. However, to date, none have been approved for use in this setting, due mainly to a lack of efficacy or unfavourable safety profiles.		In the past, attention in combatting chemotherapy resistance has focused on repurposing existing therapeutics to serve as add-on treatments to help combat chemotherapy resistance. Specifically, many kinase inhibitors have been investigated as potential combinations to enhance irinotecan response. These include sorafenib, imatinib mesylate, sunitinib, nilotinib and dasatinib. However, to date, none have been approved for use in this setting, due mainly to a lack of efficacy or unfavourable safety profiles.
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	== Valuation ==		== Valuation ==
	Edison Investment Research values Scandion Oncology at SEK586.5m or SEK18.3 per share. Edison Investment Research's valuation is based on a risk-adjusted net present value (rNPV) of SCO-101 and includes cash and cash equivalents of DKK87.97m at end-March 2022. Edison Investment Research's method includes the valuation for SCO-101 in both last-line mCRC (peak sales $295.2m, rNPV of SEK8.5 per share) and metastatic PC (peak sales $685.0m, rNPV of SEK5.8 per share) in both the US and EU5 markets, using a discount rate of 12.5%. Until management confirms its intention to treat mutant-RAS type patients through the initiation of a study in this population, given the data gathered in the CORIST study to date, Edison Investment Research only includes wtRAS patients in its valuation for mCRC. The assumptions used in Edison Investment Research's valuation are presented in Exhibit 8.		Edison Investment Research values Scandion Oncology at SEK586.5m or SEK18.3 per share. Edison Investment Research's valuation is based on a risk-adjusted net present value (rNPV) of SCO-101 and includes cash and cash equivalents of DKK87.97m at end-March 2022. Edison Investment Research's method includes the valuation for SCO-101 in both last-line mCRC (peak sales $295.2m, rNPV of SEK8.5 per share) and metastatic PC (peak sales $685.0m, rNPV of SEK5.8 per share) in both the US and EU5 markets, using a discount rate of 12.5%. Until management confirms its intention to treat mutant-RAS type patients through the initiation of a study in this population, given the data gathered in the CORIST study to date, Edison Investment Research only includes wtRAS patients in its valuation for mCRC. The assumptions used in Edison Investment Research's valuation are presented in Exhibit 8.

	~~'''Exhibit 8: Assumptions for rNPV valuation of SCO-101<ref name=":1" />'''~~


	{\| class="wikitable"		{\| class="wikitable"
	\|+		\|+'''Exhibit 8: Assumptions for rNPV valuation of SCO-101<ref name=":1" />'''
	!Indication		!Indication
	!Comments		!Comments

>Edison: /* Further studies will require fresh capital */

2022-06-22T15:10:54Z

Further studies will require fresh capital

← Older revision		Revision as of 16:10, 22 June 2022
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	'''Exhibit 1: SCO-101 development strategy'''<ref>Source: Scandion Oncology interim report Q122.</ref>		'''Exhibit 1: SCO-101 development strategy'''<ref>Source: Scandion Oncology interim report Q122.</ref>

			[[File:Image3-f037ec1ee2495554a573c0cdde896311.png]]

	The market for CRC treatment is estimated to reach $8.7bn by 2028 (EvaluatePharma) and, since Avastin (bevacizumab, Roche) went off-patent in 2019, has become more fragmented (see Exhibit 2). This market represents an attractive opportunity for SCO-101, in Edison Investment Research's view, as Edison believes Scandion could potentially establish market share for its product candidates more easily compared to indications that are dominated by one or two therapies. Additionally, many treatments for CRC (including mCRC) are already off-patent, for example irinotecan and 5-fluorouracil (the active ingredients of FOLFIRI). Edison Investment Research believes this will motivate Scandion to pursue premium pricing for SCO-101 as it would generally be used in combination with relatively inexpensive drugs.		The market for CRC treatment is estimated to reach $8.7bn by 2028 (EvaluatePharma) and, since Avastin (bevacizumab, Roche) went off-patent in 2019, has become more fragmented (see Exhibit 2). This market represents an attractive opportunity for SCO-101, in Edison Investment Research's view, as Edison believes Scandion could potentially establish market share for its product candidates more easily compared to indications that are dominated by one or two therapies. Additionally, many treatments for CRC (including mCRC) are already off-patent, for example irinotecan and 5-fluorouracil (the active ingredients of FOLFIRI). Edison Investment Research believes this will motivate Scandion to pursue premium pricing for SCO-101 as it would generally be used in combination with relatively inexpensive drugs.
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	'''Exhibit 2: Estimated CRC market to 2028'''<ref name=":0">Source: EvaluatePharma, Edison Investment Research.</ref>		'''Exhibit 2: Estimated CRC market to 2028'''<ref name=":0">Source: EvaluatePharma, Edison Investment Research.</ref>

			[[File:Image4-6ff227f569067ae2b29573f4aa4f3314.png]]



	'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''		'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''

>Edison: /* Summary */

2022-06-22T14:07:13Z

Summary

Show changes

>Edison: Created page with "== Summary == '''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which we expect crucial proof-of-concept results in..."

2022-06-21T22:50:37Z

Created page with "== Summary == '''Scandion Oncology is a Danish biotechnology company that specialises in developing drugs to reverse chemotherapy resistance. Its lead asset, SCO-101, is being investigated as an add-on therapy to existing treatments in metastatic colorectal cancer (mCRC) and unresectable pancreatic cancer (PC). Management’s clinical programme is spearheaded by the Phase II CORIST study in FOLFIRI-resistant mCRC, from which we expect crucial proof-of-concept results in..."

Show changes

← Older revision		Revision as of 16:17, 22 June 2022
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	'''Exhibit 1: SCO-101 development strategy'''<ref>Source: Scandion Oncology interim report Q122.</ref>		'''Exhibit 1: SCO-101 development strategy'''<ref>Source: Scandion Oncology interim report Q122.</ref>

	[[File:Image3-f037ec1ee2495554a573c0cdde896311.png]]		[[File:Image3-f037ec1ee2495554a573c0cdde896311.png\|600px]]

	The market for CRC treatment is estimated to reach $8.7bn by 2028 (EvaluatePharma) and, since Avastin (bevacizumab, Roche) went off-patent in 2019, has become more fragmented (see Exhibit 2). This market represents an attractive opportunity for SCO-101, in Edison Investment Research's view, as Edison believes Scandion could potentially establish market share for its product candidates more easily compared to indications that are dominated by one or two therapies. Additionally, many treatments for CRC (including mCRC) are already off-patent, for example irinotecan and 5-fluorouracil (the active ingredients of FOLFIRI). Edison Investment Research believes this will motivate Scandion to pursue premium pricing for SCO-101 as it would generally be used in combination with relatively inexpensive drugs.		The market for CRC treatment is estimated to reach $8.7bn by 2028 (EvaluatePharma) and, since Avastin (bevacizumab, Roche) went off-patent in 2019, has become more fragmented (see Exhibit 2). This market represents an attractive opportunity for SCO-101, in Edison Investment Research's view, as Edison believes Scandion could potentially establish market share for its product candidates more easily compared to indications that are dominated by one or two therapies. Additionally, many treatments for CRC (including mCRC) are already off-patent, for example irinotecan and 5-fluorouracil (the active ingredients of FOLFIRI). Edison Investment Research believes this will motivate Scandion to pursue premium pricing for SCO-101 as it would generally be used in combination with relatively inexpensive drugs.
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	'''Exhibit 2: Estimated CRC market to 2028'''<ref name=":0">Source: EvaluatePharma, Edison Investment Research.</ref>		'''Exhibit 2: Estimated CRC market to 2028'''<ref name=":0">Source: EvaluatePharma, Edison Investment Research.</ref>

	[[File:Image4-6ff227f569067ae2b29573f4aa4f3314.png]]		[[File:Image4-6ff227f569067ae2b29573f4aa4f3314.png\|600px]]


	'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''		'''Exhibit 3: Estimated PC market to 2028<ref name=":0" />'''

	[[File:Image5-ca177f6ef17ee0c8dfa1ecbf0e399de9.png]]		[[File:Image5-ca177f6ef17ee0c8dfa1ecbf0e399de9.png\|600px]]

	The second trial, PANTAX, is a Phase Ib study investigating the safety and tolerability of SCO-101 in patients with unresectable or metastatic PC as an add-on to treatment with nab-paclitaxel and gemcitabine. PC accounts for only 3% of all cancers but 7% of cancer-related deaths, due to the disease’s invasive and often incurable nature. Accordingly, the five-year survival rate for patients with PC is only 11%, dropping to 3% for patients who are diagnosed after the disease has metastasised. The PC treatment market is estimated to reach $5.3bn by 2028 (source: EvaluatePharma). However, Merck’s Keytruda (pembrolizumab) is expected to dominate the market in this period (consensus worldwide sales in 2028 of $2.7bn). Edison Investment Research notes that, as in CRC, many standard PC treatments are off-patent (eg nab-paclitaxel) and if SCO-101 can restore clinical response to these (eg nab-paclitaxel), Edison Investment Research sees an sizable opportunity for Scandion Oncology in this market.		The second trial, PANTAX, is a Phase Ib study investigating the safety and tolerability of SCO-101 in patients with unresectable or metastatic PC as an add-on to treatment with nab-paclitaxel and gemcitabine. PC accounts for only 3% of all cancers but 7% of cancer-related deaths, due to the disease’s invasive and often incurable nature. Accordingly, the five-year survival rate for patients with PC is only 11%, dropping to 3% for patients who are diagnosed after the disease has metastasised. The PC treatment market is estimated to reach $5.3bn by 2028 (source: EvaluatePharma). However, Merck’s Keytruda (pembrolizumab) is expected to dominate the market in this period (consensus worldwide sales in 2028 of $2.7bn). Edison Investment Research notes that, as in CRC, many standard PC treatments are off-patent (eg nab-paclitaxel) and if SCO-101 can restore clinical response to these (eg nab-paclitaxel), Edison Investment Research sees an sizable opportunity for Scandion Oncology in this market.
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	'''Exhibit 5: SCO-101 dual mechanism of action<ref>Source: Scandion Oncology corporate presentation.</ref>'''		'''Exhibit 5: SCO-101 dual mechanism of action<ref>Source: Scandion Oncology corporate presentation.</ref>'''

	[[File:Image6-b18deb263878259b652ac43cea6d3088.png]]		[[File:Image6-b18deb263878259b652ac43cea6d3088.png\|600px]]

	Additionally, as stated above, SCO-101 inhibits the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) to block the metabolism of chemotherapy drugs and increase systemic levels. The UGT family of enzymes work by modifying a chemotherapy drug with glucuronic acid, therefore making it more water soluble and easier to eliminate from the body. There is a body of clinical evidence that supports the role of UGTs in the development of drug resistance in multiple classes of chemotherapy agents, including alkylating agents, targeted therapies, antiangiogenics and hormonal therapies. Altogether, SCO-101’s dual mechanism acts to reverse drug resistance by increasing the level of chemotherapy drug in the body (through UGT1A1 inhibition) while simultaneously decreasing the ABCG2 mediated removal of the drug from the cell.		Additionally, as stated above, SCO-101 inhibits the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) to block the metabolism of chemotherapy drugs and increase systemic levels. The UGT family of enzymes work by modifying a chemotherapy drug with glucuronic acid, therefore making it more water soluble and easier to eliminate from the body. There is a body of clinical evidence that supports the role of UGTs in the development of drug resistance in multiple classes of chemotherapy agents, including alkylating agents, targeted therapies, antiangiogenics and hormonal therapies. Altogether, SCO-101’s dual mechanism acts to reverse drug resistance by increasing the level of chemotherapy drug in the body (through UGT1A1 inhibition) while simultaneously decreasing the ABCG2 mediated removal of the drug from the cell.
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	First-line therapy for mCRC relies heavily on 5-fluorouracil (5FU)-based chemotherapy regimens, often supplemented with targeted therapies (should a molecular driver be present) and/or biologic agents (eg vascular-endothelial growth factor A, VEGF, targeting monoclonal antibody, bevacizumab). Later lines of therapy will also generally be formed around modification of 5FU-based regimens. A common treatment in this setting is FOLFIRI, a chemotherapy regimen consisting of leucovorin calcium, 5-fluorouracil and irinotecan. One of the active ingredients of this regimen, irinotecan, is a prodrug of the potent topoisomerase I inhibitor SN-38. Drugs of this class kill tumour cells by inhibiting DNA repair processes. The development of resistance to irinotecan chemotherapy through ABCG2 efflux pump overexpression and UTG1A1 activity is well documented, thus Scandion Oncology has identified FOLFIRI as a potentially attractive combination therapy for SCO-101. Indeed, analysis of CORIST patients treated with SCO-101 and irinotecan in Part I of CORIST has shown dramatically increased plasma levels of SN-38 at a 90mg/m2 dose when compared to SN-38 data from treatment with irinotecan at 180 mg/m2 (based on patients outside the CORIST study, Exhibit 6), although Edison Investment Research cautions that there are limitations to comparing data from different studies.		First-line therapy for mCRC relies heavily on 5-fluorouracil (5FU)-based chemotherapy regimens, often supplemented with targeted therapies (should a molecular driver be present) and/or biologic agents (eg vascular-endothelial growth factor A, VEGF, targeting monoclonal antibody, bevacizumab). Later lines of therapy will also generally be formed around modification of 5FU-based regimens. A common treatment in this setting is FOLFIRI, a chemotherapy regimen consisting of leucovorin calcium, 5-fluorouracil and irinotecan. One of the active ingredients of this regimen, irinotecan, is a prodrug of the potent topoisomerase I inhibitor SN-38. Drugs of this class kill tumour cells by inhibiting DNA repair processes. The development of resistance to irinotecan chemotherapy through ABCG2 efflux pump overexpression and UTG1A1 activity is well documented, thus Scandion Oncology has identified FOLFIRI as a potentially attractive combination therapy for SCO-101. Indeed, analysis of CORIST patients treated with SCO-101 and irinotecan in Part I of CORIST has shown dramatically increased plasma levels of SN-38 at a 90mg/m2 dose when compared to SN-38 data from treatment with irinotecan at 180 mg/m2 (based on patients outside the CORIST study, Exhibit 6), although Edison Investment Research cautions that there are limitations to comparing data from different studies.

	'''Exhibit 6: SN-38 plasma concentrations in CORIST patients<ref>Source: Scandion Oncology CMD update.</ref><br />'''[[File:Image7-c31e427382287da7a43068acd0e06507.png]]		'''Exhibit 6: SN-38 plasma concentrations in CORIST patients<ref>Source: Scandion Oncology CMD update.</ref><br />'''

			[[File:Image7-c31e427382287da7a43068acd0e06507.png\|600px]]

	While plasma concentrations in the CORIST patients were dramatically higher when compared to patients treated only with irinotecan (using data compiled from separate studies), Edison Investment Research notes that high plasma levels of SN-38 do not necessarily correlate with a clinical effect, especially in ABCG2 driven resistance. However, this data does provide support for the SCO-101/FOLFIRI combination with the lower 90mg/m2 CORIST dosing regimen for irinotecan (compared to 180mg/m2 commercial norm).		While plasma concentrations in the CORIST patients were dramatically higher when compared to patients treated only with irinotecan (using data compiled from separate studies), Edison Investment Research notes that high plasma levels of SN-38 do not necessarily correlate with a clinical effect, especially in ABCG2 driven resistance. However, this data does provide support for the SCO-101/FOLFIRI combination with the lower 90mg/m2 CORIST dosing regimen for irinotecan (compared to 180mg/m2 commercial norm).
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	'''Exhibit 7: Preclinical SCO-101 data in combination with paclitaxel'''<ref>Source: Scandion Oncology BACR presentation September 2021.</ref>		'''Exhibit 7: Preclinical SCO-101 data in combination with paclitaxel'''<ref>Source: Scandion Oncology BACR presentation September 2021.</ref>

	[[File:Image8-d2f0ab9ac32701491636345b4497b7bb.png]]		[[File:Image8-d2f0ab9ac32701491636345b4497b7bb.png\|600px]]

	=== SCO-101 could be first in class in chemotherapy resistance ===		=== SCO-101 could be first in class in chemotherapy resistance ===
	In the past, attention in combatting chemotherapy resistance has focused on repurposing existing therapeutics to serve as add-on treatments to help combat chemotherapy resistance. Specifically, many kinase inhibitors have been investigated as potential combinations to enhance irinotecan response. These include sorafenib, imatinib mesylate, sunitinib, nilotinib and dasatinib. However, to date, none have been approved for use in this setting, due mainly to a lack of efficacy or unfavourable safety profiles.		In the past, attention in combatting chemotherapy resistance has focused on repurposing existing therapeutics to serve as add-on treatments to help combat chemotherapy resistance. Specifically, many kinase inhibitors have been investigated as potential combinations to enhance irinotecan response. These include sorafenib, imatinib mesylate, sunitinib, nilotinib and dasatinib. However, to date, none have been approved for use in this setting, due mainly to a lack of efficacy or unfavourable safety profiles.